Atypical Chest Pain Syndrome in Patients With Breast Implants

LEE B. LU, BS, BRITTA OSTERMEYER SHOAIB, MD, and BERNARD M. PATTEN, MD, Houston, Tex

ABSTRACT: Eleven patients, aged 36 to 55 years, with silicone breast implants had episodes of severe chest pain similar to heart attacks 6 weeks to 7 years after breast implantation; one patient had a severe attack 1 month after explantation. The chest pain, which was not related to physical exertion, lasted from 15 minutes to 4 days, and descriptions of it varied from a "pressing" type of pain to "stabbing" pain with radiation to the shoulders, left arm, and jaw. The associated symptoms were diaphoresis, nausea, vomiting, dyspnea, and palpitations. All of the patients had a normal electrocardiogram (ECG) with the exception of one, whose ECG showed nonspecific ST changes. Ten had cardiac evaluations, all of which yielded normal results. All had implant removal, and five were found to have at least one ruptured implant. Nine had an implant capsule biopsy; all had chronic inflammatory rinds, and five had free silicone in tissue whether or not the implants were ruptured. All eight who had a pectoralis major muscle biopsy had abnormal results: (neurogenic atrophy [six], fasciitis [three], myositis [one], chronic inflammation [one], free silicone [one], and neuroma [one]). We concluded that silicone breast implants may cause an atypical chest pain syndrome, probably due to local inflammatory reactions and neuroma formation.

 

Reprinted from the Southern Medical Journal, Journal of the Southern Medical Association, Volume 87, Number 10,
October 1994, Pages 978-984, Copyright © 1994 by Southern Medical Association, Birmingham, Alabama

 

 

AUGMENTATION MAMMAPLASTY was first practiced in Japan during World War II, when Japanese women enlarged their breasts by direct injections of paraffin or silicone.¹ In the United States, since the silicone envelope-type prosthesis was introduced by Cronin and Gerow² in 1962, breast implants have been widely used. According to the Food and Drug Administration (FDA), approximately 1 million women in the United States have received silicone breast implants.³ Silicone breast implants have been associated with many complications, including fibrous capsule contracture,^4,5 implant rupture,^6,7 gel bleed,^8-10 silicone migration,^8,11-13 human carcinogenicity,^14-16 (degradation of polyurethane  into  2,4  diaminotoluene,  a  known  carcinogen), ^17-21 autoimmune  and  connective  tissue  diseases, ^22-29 and  neurologic   problems.^30-32 As a consequence of these reported complications and the failure of breast implant manufacturers to provide the FDA with sufficient safety and efficacy data, the FDA ordered a moratorium on January 6, 1992, on the further distribution of the silicone gel implants.³

      From 1985 to the present, almost 1,500 patients have been referred to us for the management of neurologic symptoms occurring after insertion of silicone breast implants. While evaluating their cases, we discovered that some of the patients had had episodes of severe chest pain with associated symptoms of nausea, vomiting, diaphoresis, and dyspnea resembling the symptoms of heart attack and requiring evaluation for possible myocardial infarction. Despite the initial workup for a possible infarct, these women were eventually determined to have had noncardiac chest pain. In this article, we describe the clinical symptoms and laboratory findings in the cases of 11 patients with an atypical chest pain syndrome and silicone breast implants; all of the patients were referred to us for evaluation of neurologic symptoms occurring after implantation of silicone breast implants.

METHODS

 

The study subjects were 11 patients referred to us for evaluation of neurologic symptoms occurring after implantation of silicone breast implants. Each gave a history and had a physical examination, completed a questionnaire about implants and symptoms, and received laboratory testing, including a complete blood count, urinalysis, SMA-15, and serum protein electrophoresis. The subjects were also tested for quantitative immunoglobulins, complements C3 and C4, antinuclear antibodies (ANA), antimyelin associated glycoprotein antibodies (anti-MAG), rheumatoid factor, antiganglioside GM₁ antibodies (anti-GM₁) and antisulfatide antibodies. All patients had implant removal. At time of removal, 9 patients had an implant capsule biopsy, and 8 had a pectoralis major muscle biopsy. Formalin sections obtained from the implant capsule biopsy were stained with hematoxylin and eosin and read by a pathologist at the Methodist Hospital. Frozen sections of muscle tissue were stained with nicotinamide adenine dinucleotide (NADH)- tetrazolium reductase, myofibrillar adenosinetriphosphatase at a pH of 9.4, and modified Gomori's trichrome.

In addition, we reviewed any available cardiac evaluation done by other physicians and medical records of previous emergency department admissions. All patients were interviewed personally at the time of presentation and again at a later date via telephone. They were all asked to describe the attack of chest pain and were questioned regarding risk factors for coronary artery disease and possible noncardiac causes of chest pain such as peptic ulcer, indigestion, esophageal reflux, hiatal hernia, esophageal diseases, trauma to the chest and psychosomatic disorders.

CASE REPORTS

 

Patient 1. A 44-year-old woman was referred to us by her family physician in Indiana for evaluation of breast implant problems. In 1977 she had a saline breast implant on the left for Poland's syndrome. Within the same year, she had a closed capsulotomy to release capsular contracture. In 1979 she had a mastopexy on the right with insertion of a saline breast implant. In 1985 both of the saline implants were replaced by polyurethane-coated silicone gel implants made by Surgitek (Racine, Wis).

Six months after the first implantation, muscle pain, burning and discomfort developed in the shoulders, hips, and knees. Extreme fatigability also developed, to the point that she could not dress herself, as well as joint pain, joint swelling and stiffness, dry eye syndrome, skin rash, Raynaud's phenomenon, numbness of arms, hands, and fingers, and memory deficits. In 1991 Graves' disease developed, and in 1992 she sought treatment for local chest problems, including tenderness, itching, a burning sensation, and swelling in both breasts. She was admitted for evaluation of these symptoms. The implants were removed but revealed no evidence of rupture. Biopsy specimens of the implant capsules showed chronic inflammatory cells with numerous foamy histiocytes and refractile translucent foreign material consistent with silicone. Pectoralis major muscle biopsy showed neurogenic atrophy.

On December 19, 1992, while sitting in her living room watching television, the patient experienced acute onset of severe chest pain associated with diaphoresis, shortness of breath, nausea, and vomiting. The pain was described as "pressurelike" and radiated bilaterally to the shoulders and to the left arm. She thought she was having a heart attack but could not identify any relieving or aggravating factor.
     After the chest pain persisted for 3 hours, she went to the Methodist Hospital emergency department. According to the patient, she had often had chest pain since receiving the breast implants, but it had never been as severe and intense as this episode. She had had heart catheterization to investigate the chest pain, and the results were normal. She had no psychologic problems, hypertension, or diabetes. Even though she had no previous history of gastrointestinal disease, she had an upper gastric endoscopy, which yielded normal results. The family history was significant in that her father had died of myocardial infarction at the age of 62. She did not smoke. She had been taking conjugated estrogens (Premarin), 2.5 mg daily, since having a hysterectomy in 1978. On admission to the emergency department, blood pressure was 130/80 mm Hg, and other vital signs were stable. The chest was clear on auscultation. The heart rate and rhythm were regular, and S₁ and S₂ were normal, without any murmur or gallop. Nitroglycerin was administered immediately but with no observable relief of symptoms. Electrocardiogram (ECG) showed sinus tachycardia with no acute changes. Testing for total levels of creatine kinase, creatine kinase MB, and lactate dehydrogenase was done serially over 3 days; all tests yielded normal results. A normal two-dimensional echocardiogram was obtained with an ejection fraction of 55%. The chest pain had resolved by itself within 24 hours after admission. Since the December 1992 admission for chest pain, the patient has had no recurrence of any similar chest pain.

Patient 2. A 55-year-old woman came to our clinic in February 1992 for evaluation of symptoms related to breast implants. The patient had had a right modified mastectomy in November 1987 and a left total mastectomy in July 1988 for intraductal carcinoma of both breasts. Subsequently, in November 1988, bilateral breast reconstruction was done using polyurethane-covered silicone gel breast implants made by Surgitek. In January 1989 she had a left capsular contracture release by closed capsulotomy. In spring 1989 local problems, such as breast tenderness, pain, and tightness bilaterally, began to develop, and she had an open capsulectomy for capsular release in the left breast in October 1989. In 1990 muscle aches and pain, muscle weakness and fatigability, joint pain and stiffness, headache, dry eyes, dry mouth and dry vagina (sicca complex), memory problems, and elevated temperatures developed.

     In the same year, while working as a bank teller, she had an attack of severe chest pain. The pain lasted 3 days and was described as a "feeling of tightness" in the midchest that radiated to the left shoulder and back. Accompanying symptoms included diaphoresis and a "smothering" feeling. She could not identify any relieving or aggravating factor. She went directly to the emergency department. Her cholesterol level was 234 mg/dL; otherwise, she had no risk factors for coronary artery disease. She did not smoke and had no history of hypertension or diabetes. The family history was negative for coronary artery disease. She had no history of gastrointestinal problems, psychologic problems, or trauma to the chest. On admission to the emergency department, her systolic blood pressure was in the 200s; all other vital signs were normal. On physical examination, lungs were clear to auscultation, heart rate and rhythm were regular, and S₁ and S₂ were normal, without murmur or gallop. Nitroglycerin gave no relief of pain. ECG was normal, and cardiac enzyme levels were all within normal ranges. Heart catheterization yielded normal studies of coronary arteries, left ventricular function, and the thoracic aorta; there was no evidence of inducible coronary vasospasm. She was discharged, and nifedipine was prescribed for blood pressure control. Since discharge, she has had no recurrent severe chest pain but has continued to have persistent local tenderness and pain in both breasts.

In 1991 the Surgitek implants were removed, and both implants were found to be ruptured. She received replacement silicone gel implants made by Dow Corning (Midland, Mich) but continued to have chest pain and systemic symptoms. She was then referred to us for further evaluation of her problems. She had bilateral breast implant removal with left axillary lymph node excision. The implants were found to be intact, and the lymph nodes showed varying degrees of sinus histiocytosis. Biopsy of the implant capsule showed chronic inflammation. Biopsy of the pectoralis major muscle showed neurogenic atrophy.

RESULTS

Patient Demographics

 

The patients ranged in age from 36 to 55 years. The mean age at time of first implantation was 36 years (range 29 to 52) (Table 1). The mean age at onset of the chest pain was 40 years (range 34 to 53). The median latency period between implantation and development of the chest pain was 4 years. The types of breast implants our patients had received and the reasons for implantation are summarized in Table 1. Five patients received more than one pair of implants due to local complications with the implants.

Local and Systemic Symptoms

 

All patients had local problems with their breasts, including capsular contracture, tenderness, soreness or pain, heat and swelling, infections, and discharge or numbness of the nipples. They all had chest pain, thought to be due to a possible myocardial infarction. Implant capsule biopsy specimens showed chronic inflammation consisting of foamy histiocytes and plasma cells in all patients who had a biopsy and foreign body giant cells and foreign material consistent with silicone in some (Table 1). Pectoralis biopsy specimens were abnormal for all eight patients who had biopsies (Table 1).

In all cases, systemic symptoms developed, including myalgia, muscle weakness and fatigue, arthralgia, joint swelling and stiffness, skin rash, headache, dry mouth, dry eyes, memory problems, hair loss, sensitivity to sunlight, and numbness and a tingling sensation in the extremities. All patients were admitted to the hospital for investigation of their systemic symptoms and were found to have peripheral or central nervous system disease and circulating antibodies such as ANA, anti-GM₁, anti-MAG, or antisulfatide. Six patients had been admitted to the hospital previously for evaluation of chest pain.

Chest Pain and Evaluation of Chest Pain

 

The time of onset of the chest pain varied from 6 weeks to 7 years after breast implantation; one patient had a severe attack 1 month after explantation (Table 2). In all cases, the chest pain came on suddenly when the patients were not physically exerting themselves. The type of pain varied from a "pressing" type of pain to "stabbing" pain. The pain was located mostly in the midchest with radiation to the shoulders, left arm, back, and jaw and lasted 15 minutes to 4 days. Associated symptoms included diaphoresis, nausea, vomiting, dyspnea, and palpitations. Five of the six patients who were admitted to the hospital for evaluation of possible myocardial infarction got no relief of chest pain from nitroglycerin. Patient 11 reported mild improvement in the chest pain after using a nitroglycerin patch and massaging her breasts. Her cardiologist told her that she did not need the patch. The other five patients never received nitroglycerin.

 

All patients had cardiac evaluations, except for patient 4, who had only an EGG because her physician believed that her chest pain was not of cardiac origin. In her case, physical evaluation just before breast implantation showed that her heart was in excellent condition because she was able to participate in water sports and exercise strenuously without any problems. As a 34-year-old woman with no family history of cardiac disease and a low cholesterol level, she was in a low-risk group for cardiac disease. All patients had normal ECGs during and after the attack of chest pain, except for patient 11; at one point her EGG showed nonspecific ST changes, but two dobutamine thallium 201 perfusion scintigraphy tests yielded normal results. Her cardiologist did not think the changes were of clinical significance and did not indicate ischemic disease. Five patients had exercise treadmill tests; all five yielded normal results. Six patients had two-dimensional echocardiograms with ejection fractions of 55% to 70% and no abnormal findings, except for patient 8, who was found to have mild mitral valve prolapse. Four patients had a dobutamine thallium 201 perfusion scintigraphy study with normal results. Patient 9 had 24-hour Holter monitoring with negative results. Patient 5 had a multiple gate acquisition analysis (MUGA) showing a left ventricular ejection fraction of 74% and normal wall motion. Three patients had heart catheterization with normal results. The four patients who went to the emergency department had normal levels of cardiac enzymes; the studies, done serially over 3 days, included creatine kinase, creatine kinase MB, and lactate dehydrogenase. After tests for heart disease yielded negative results, our patients' cardiologists classified their chest pain as "noncardiac."

 

After implant removal, the symptoms lessened considerably in nine patients and subsided in two (Table 3). Only patient 1 had another attack shortly after having explantation, but her symptoms subsequently improved as well.

Evaluation of Risk Factors for Coronary Artery Disease and Possible Sources of Noncardiac Chest Pain

 

None of the patients had a history of angina pectoris, dyspnea on exertion, or myocardial infarction before breast implantation. None had diabetes mellitus. Four patients were found to have elevated cholesterol levels (Table 3). Three patients smoked cigarettes (5 to 12 pack-years). Four had a family history of coronary artery disease. Six patients had a history of surgical menopause; however, all of them had been receiving hormone replacement therapy. Of the five patients who had upper gastric endoscopy, one had reflux and hiatal hernia, one had mild esophagitis, two had a hiatal hernia, and one had normal results (Table 3). The remaining six patients had no history of gastrointestinal problems. None of the patients had a history of chest trauma or psychosomatic disorders.