What Happened to the Bismuth Line?

Qing C. Zeng, D.D.S.; Louis Mandel, D.D.S.

ABSTRACT

The historical use of bismuth in the treatment of syphilisis reviewed. Attention is called to a patient’s development of dark blue/black bismuth deposits that involved the marginal gingiva and lateral ventral tongue surface. A mechanism is described to explain the presence of bismuth deposition in these two oral areas. The explanation for the deposition is based on modern concepts of the pathophysiology of inflammation.

Before penicillin was discovered to be a safe and efficacious treatment for syphilis, many treatment modalities were promulgated, each with its own adverse effects. In the late 19th and early 20th centuries, when syphilis affected a significant portion of the population, mercury was the treatment of choice. Many mercurial preparations were utilized, but it soon became apparent that the drug’s serious side effects outweighed its benefits. Patients often developed kidney failure, neuropathies and mouth ulcers. Mercury poisoning also could occur and lead to death. 1,2

Following the discovery of the causative spirochete, Ehrlich’s investigations resulted in the use of arsenics for the treatment of syphilis. 3 Ehrlich was awarded the Nobel Prize for the introduction of the therapeutic arsenical Salvarsan. Salvarsan proved to be more effective for the treatment of syphilis than the previously used mercury formulations. Nevertheless, it, too, caused side effects, and soon reports of liver failure and seizures were received. 3

The more successful use of bismuth in the treatment of syphilis was first advocated by Balzer in 1889 and then confirmed and popularized by Salzerac and Levaditi in 1921. 4 Almost immediately after the introduction of bismuth for syphilis therapy, it was widely adopted by syphilologists as a substitute for mercury, and for patients who had problems with the arsenicals. 4,5 Bismuth proved to be an effective agent for the treatment of congenital and acquired syphilis. 6 Unfortunately, bismuth also proved to have side effects with its prolonged use. These included excessive salivation, stomatitis, diarrhea and albuminuria. 5 The side effects were usually transient and hardly necessitated discontinuing treatment. 7

A major objection of patients focused on the formation of a blue/black line along the gingival margins. The bismuth gingival line was first reported by Balzer in 1889, and then in 1921 by Salzerac and Levaditi. 4 Reports indicated that 56% to 70% of patients undergoing bismuth treatment developed this gingival manifestation of bismuth therapy. 8-10 The line was also observed when the bismuth was administered for conditions such as chronic discoid lupus erythematosus, lichen planus, scleroderma and granuloma annulare. 10 An increased bismuth line incidence is directly correlated with increased dosages of bismuth. 11 Of interest is the fact that the gingival lines were shown to disappear in about one month after bismuth treatment ended. 11

Although many investigators have written about the line’s clinical presentation and histopathology, its etiology has not been clearly defined. The discoloration usually appears along the gingival margin of the teeth, particularly the mandibular incisors, and at any time during treatment. 6 Silverman 9 reported that the lines appear where there is pre-existing inflammation of the gingival tissues. He had observed that the marginal gingival bismuth pigmentation was first seen adjacent to heavy deposits of calculus, ill-fitting crowns and bridges, or around restorations that impinge upon the gingiva. The greater likelihood of a tissue irritating calculus build-up in the lower anterior region was thought to explain the commonly observed bismuth line presentation in this region. 10 Poor oral hygiene and gingival inflammation have often been noted to be associated with the line’s presence. 4,6,9-12

It is believed that the interaction of bismuth with hydrogen sulfide in the oral cavity forms bismuth sulfide. 4,10,11,13 The hydrogen sulfide is generated as a result of the decomposition of food and bacteria, 10 and may explain the halitosis often associated with the onset of bismuth lines. Similarly, Burton’s line, a clinical sign of chronic lead poisoning, results from the reaction of sulfur ions in the oral cavity with lead. 13 Histopathological examination and microchemical analysis have demonstrated that the bismuth, in the form of bismuth sulfide, is present in the endothelial walls of capillaries and also in the surrounding connective tissue. 8,10,12

Figure 1. Bismuth line involves inflamed marginal gingiva of mandibular and maxillary teeth.

Through the courtesy of Dr. Edward Zegarelli, an old pictorial record of a patient, who had undergone bismuth treatment for syphilis, was made available. An examination had revealed the characteristic bismuth line along the gingival margins of the dentition (Figure 1). Both the lingual and buccal gingival margins were affected. Calculus and debris along the gingival margins and a marginal gingival inflammation were also noted. In a more surprising presentation of bismuth deposition, the patient also had the characteristic bismuth deposition and discoloration on the right lateral ventral surface of the tongue (Figure 2). It was obvious from the oral examination that this portion of the patient’s tongue was being traumatized by the fractured and unrestored margins of the carious lower right first molar. It is this additional presence of bismuth precipitation in the tongue that allows us to postulate a mechanism for the formation of the bismuth line based on the pathophysiology of inflammation.

Inflammation can be a response to many challenges to the human body. It is designed to combat the effect of any irritant, bacterial or traumatic, and to initiate potentiate tissue repair. As previously reported by investigators of bismuth lines, inflammation of the gingival tissues is closely associated with this sign. 4,6,9-12 Our patient had both a gingival inflammation (marginal gingivitis) from a bacterial infection originating from the gingival sulcus, and a traumatically incited inflammation from the irritation caused by the margins of the carious molar. Whether the inflammation is from bacteria or trauma, the classic inflammatory response is vasodilation, increased vessel permeability and exudation of protein-rich plasma. 14

The inflammatory process involves arterioles, capillaries and the opening of new microvascular beds. Edema from the increased capillary permeability is an integral aspect of inflammation. The edema results from the transvascular flux of proteinrich fluid from the intravascular component to the interstitium, and is caused by vasoactives, such as histamine and bradykinin. 14 The permeability of capillaries and venules for both water and protein molecules is increased as a result of these factors. The loss of plasma proteins decreases intravascular osmotic pressure. The combined effects of the increase in vascular permeability, increase in capillary hydrostatic pressure, and fall in plasma osmotic pressure induce a gradient of fluid and protein flow into the inflamed interstitium. 14 It is likely that this gradient of fluid and protein flow created by inflammation allows the precipitation of bismuth into the capillary walls and its escape and deposition into the subepithelial layers of the oral tissue. The enhanced vascularity and vessel permeability enabled bismuth to collect in greater concentration in our patient’s areas of inflammation. The increased concentration of bismuth along the gingival margins and along the traumatized tongue area react with the sulfide in the oral environment, and resulted in the gingival bismuth line and simultaneously discolored the physically inflamed region of the tongue.

Conclusion We briefly reviewed the history of the use of bismuth for the treatment of syphilis. Emphasis was placed on a bismuth side effect, a dark blue/black line involving the marginal gingivae. Bismuth deposition was also noted in the tongue. It was these oral bismuth depositions, from two different causes of inflammation, that offer an explanation for its occurrence that fits into the modern concept of the pathophysiology of the inflammatory process.

The authors report no commercial associations, current and within the past five years, that might pose a potential, perceived or real conflict of interest. Queries about this article can be sent to Dr. Mandel at lm7@columbia.edu.

REFERENCES

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Dr. Zeng

Qing C. Zeng, D.D.S., was a fourth-year student at Columbia University College of Dental Medicine and a research assistant in the college’s Salivary Gland Center, New York, NY. He is a resident, oral and maxillofacial surgery, University of Alabama, Birmingham.

Dr. Mandel

Louis Mandel, D.D.S., is director, Salivary Gland Center, associate dean and clinical professor, oral and maxillofacial Surgery, Columbia University College of Dental Medicine, New York, NY.

What Happened to the Bismuth Line?