References survey of the literature and a statistical study. Am J Cancer 16: 1358, 1932

1. Billroth T: Allgemeine chirurgische Pathologie und Therapie in 51 Vorleungen: Ein Handbuch fur Studierende und Arzte Auf Berlin, G Reimer. 1889

2. Warren S, Gates 0: Multiple primary malignant tumors.

3. Kirikae I: Four cases of multiple primary malignant tumors. Jpn J Otol 68:528. 1965

4. Kitabatake T: Investigation on double cancers with case re- ports and statistic consideration. Jpn J Cancer Clin 6:337, 1960

J Oral Maxillofac Surg

45:264-266. 1967

Spontaneous Tooth Exfoliation and Osteonecrosis Following a Herpes Zoster

Infection of the Fifth Cranial Nerve

RESA MOSTOFI, DMD,* HUGH MARCHMONT-ROBINSON, DDS,t AND STEVEN FREIJE, DDS$.

The first case of osteonecrosis of alveolar bone associated with a herpes zoster (HZ) infection of the trigeminal nerve was reported by Gonnett in 1922.‘,* At that time, the development of this con- dition was thought to involve the mandible of el- derly patients exclusively. In 1976, Chenitz re- ported osteonecrosis of the maxilla following a HZ infection in a 15year-old male who was suffering from stage IV Hodgkin’s disease.3 Most of the re- ported cases of osteonecrosis associated with HZ infections have been in elderly patients or those with altered immune systems due to underlying dis- ease or related treatment. Recently, however, a case of osteonecrosis following a HZ infection was reported in a 12-year-old girl without any under- lying disorders.4

Osteonecrosis following a HZ infection often presents as a painless spontaneous exfoliation of teeth in the involved area. This usually occurs after the acute phase of the infection has subsided. The pathogenesis of the osteonecrosis is unclear, al- though an alteration of the vascular supply to the affected bone has been postulated. To date, several cases of osteonecrosis of the mandible or maxilla

* Assistant Professor and Head, Department of Pathology and Radiology, The University of Chicago, Zoller Dental Clinic, Chicago, Illinois.

t Assistant Professor and Director, Department of Oral and Maxillofacial Surgery, The University of Chicago, Zoller Dental Clinic, Chicago. Illinois.

$ Oral Surgery Resident, Mount Sinai Hospital, Cleveland. Ohio.

Address correspondence and reprint requests to Dr. Mostofi: Division of Biological Sciences, The University of Chicago. Zoller Dental Clinic. Chicago, IL 60637.

0278-2391/87 $0.00 + .25

associated with a HZ infection have been reported, of which seven have appeared in the English litera- ture.3-9 A case of spontaneous exfoliation of teeth and osteonecrosis following HZ infection of the tri- geminal nerve is reported in a patient under treat- ment for chronic myelogenous leukemia.

Report of a Case

A S&year-old, non-English speaking woman had been followed as an outpatient for three weeks for a very painful and extensive HZ infection on the right side of her face that included her ear, forehead and scalp. The pa- tient’s medical record contained a seven-year history of chronic myelogenous leukemia that was well controlled. She had been maintained on doses of myleran (2 mg bid) and allopurinol (300 mg qid). Additional to her leukemia, she had a IO-year history of mitral stenosis, with concom- itant left heart failure and cardiomegally. for which she was being treated with inderol (20 mg tid), digoxin (0.25 mg qid) and coumadin.

After three weeks, healing of the HZ lesions was no- ticed (Fig. 1). However, 10 days later the patient returned because of persistent pain on the lower right side of her face. She related that four days previously three of her lower teeth had fallen out. The patient was referred to the oral and maxillofacial surgery clinic for consultation.

The intraoral examination revealed exposed alveolar bone in the area of missing teeth numbers 25-27, with the presence of purulent exudate; mobility of tooth number 24; and multiple ulcerated lesions on the right buccal mu- cosa and soft palate (Fig. 2). White plaques were noted on her posterior pharynx and the base of her tongue. These plaques were easily wiped off with gauze leaving a raw bleeding surface. A clinical diagnosis of candidiasis was cytologically confirmed. Radiographic examination revealed unhealed sockets of teeth 2.5-27 and early se- questration of an area of the alveolar bone extending from the right mental foramen to the midline, including tooth number 24 (Fig. 3). The examination also revealed generalized mild to moderate bone loss due to periodon- titis. A provisional diagnosis of osteomyelitis with spon-

264

MOSTOFI ET AL.

FIGURE 1 (top). Clinical appearance of the patient three weeks after development of skin eruptions affecting the distri- bution of the third branch of the trigeminal nerve.

FIGURE 2 (b&tom). Intraoral photograph showing the site of the exfoliation of teeth numbers 21. 22. 23. Note exposed necrotic alveolar bone and inflamed gingiva.

265

taneous exfoliation of teeth secondary to a HZ infection of the fifth cranial nerve was reached.

The patient was admitted to hospital for prophylactic intravenous antibiotics and adjustment of her medication prior to a sequesterectomy and extraction of tooth number 24. She was prescribed an antifungal rinse for her intraoral candidal infection.

Following adjustment of her medication and determina- tion that her coagulation and bleeding times were within normal limits, the sequesterectomy was performed under intravenous sedation and local anesthesia. The bone was removed until normal bleeding tissue was encountered. Tooth number 24 was extracted and an alveoloplasty was performed. The envelope flap was closed with inter- rupted 3-O silk sutures. During follow-up appointments healing was noted to be progressing normally (Fig. 4).

Discussion

The herpes zoster virus causing shingles has been equated with the varicella zoster virus that has been identified as the infectious agent in chick- enpox. The clinical difference between these two infections are the patient age, and the fact that chickenpox is a generalized vesicular eruption whereas shingles follows a particular derma- tome.6J0J1 Several authors have suggested that fol- lowing a varicella zoster virus infection, the virus remains in a latent state within the host and can be reactivated by physical or emotional stress at a later date, when it would be referred to as a HZ infection.7~9J2-14 An alternative suggestion is that the HZ infection is a primary infection of the sen- sory nerve ganglia in individuals with partial cross- immunity from an earlier varicella zoster infec- tion.5J2 The HZ virus may infect the sensory por- tion of the dorsal root ganglion of the spinal cord,

FIGURE 3 (top). Peri- apical radiographs showing the unhealed sockets of the exfoliated teeth, involve- ment of tooth number 24, and early sequestration (arrows) of the alveolar bone.

FIGURE 4 (bottom). Periapical radiographs showing resolution of the osteomyelitis after seques- trectomy and alveoloplasty were performed.

266 EXFOLIATION AND OSTEONECROSIS FOLLOWING HZ INFECTION

the extramedullary ganglia of the cranial nerves, or the motor portion of the geniculate ganglion of the facial nerve. In cases where the geniculate ganglion of the facial nerve becomes infected, the clinical manifestations are hemifacial paralysis and xero- stomia. This condition is termed the Ramsay Hunt syndrome. l5

The incidence of HZ infection has been reported to be 5.4% of the population, with a greater ten- dency to involve older individuals and those with a malignancy and related treatment.“J6J7 A HZ in- fection generally presents clinically as a low-grade fever, and a tingling and/or puritis of the skin and mucosa followed quickly by the appearance of classic vesicles along the area innervated by the in- volved nerve. The histopathologic characteristics of the HZ viral infection are indistinguishable from those of the varicella zoster infection. Because these features are not specific for the HZ virus, diagnosis depends on viral cultures and the clinical features.14,15,‘* Vesicles are not readily seen in- traorally because of their early rupture. The lesions usually heal without scarring in approximately 7- 14 days.

The HZ infection can occasionally cause osteo- necrosis, either by affecting the innervation of the periosteum or by a direct vasculotropic effect of the virus,2,3,6,19 both of which lead to alteration of the blood flow to the affected area. The role of vascular alteration in the development of osteonecrosis is further supported by the fact that osteonecrosis usually occurs in patients with compromised vascu- larity because of aging, irradiation, or chronic in- flammation. “,16

In reviewing reported cases, several points seem consistent. All but two patients reported were over the age of 4 1, with an average age of 50. The age of those cases with no obvious predisposing disease averaged 58. In general, the younger the patient with osteonecrosis due to a HZ infection, the more serious is the patient’s underlying disease.

One of the earliest signs of osteonecrosis of the jaw bones associated with a HZ infection is sponta- neous exfoliation of teeth prior to the overt signs of osteonecrosis. In non-viral osteonecrosis, however, dental pain usually heralds the exfoliation of teeth. This suggests that the periosteal blood flow is al- tered in the HZ infection, leading to necrosis of the periodontal ligament and exfoliation of the tooth prior to the development of alveolar necrosis.2,3J8

In the case reported, the patient’s chronic my- elogenous leukemia and treatment with cytotoxic chemotherapy may have predisposed her to con- tracting a HZ infection. The viral infection then led to a transient ischemia which may in turn have con- tributed to the development of osteonecrosis. This

case illustrates the potential sequela in debilitated patients contracting a HZ infection and the impor- tance of early recognition and prevention of further complications.

Summary

Spontaneous exfoliation of teeth and osteone- crosis of the alveolar bone are rare complications of HZ infection that usually follow the acute phase of infection. Awareness of osteonecrosis associated with secondary HZ infection is important for early detection and treatment of the condition to prevent further complications, particularly in high-risk pa- tients.

References

1. Dechaume M, Descrozailles C, Garlopeau F, et al: Necrose mandibulaire localisee au decors d‘un zona du trijumeau. Rev Stomatol 56516, 1955

2. Delaire J, Billet J: Deux nouvelles observations de necrose alveolaire au decor d’un zona du nerf maxillarie inferieur. Rev Stomatol 60:550, 1959

3. Chenitz JE: Herpes zoster in Hodgkin’s disease: unusual oral sequelae. J Dent Child 43:184, 1976

4. Garty B. Dinari Cl, Sarnet H. et al: Tooth exfoliation and osteonecrosis of the maxilla after trigeminal herpes zoster. J Pediatr 106:71, 1985

5. Cooper JC: Tooth exfoliation and osteonecrosis of the jaw following herpes zoster. Br Dent J 143:297, 1977

6. Hall HD, Jacobs JS. O’MaIIoy JP: Necrosis of maxilla in patients with herpes zoster. Oral Surg 37:657. 1974

7. Hudson CD, Vickers RA: Clinicopathologic observations in prodromal herpes zoster of the fifth cranial nerve. Oral Surg 31:494, 1971

8. Wright WE, Davis ML. Geffen DB, et al: Alveolar bone ne- crosis and tooth loss: a rare complication associated with herpes zoster infection of the fifth cranial nerve. Oral Surg 56:39. 1983

9. Vickery IM, Midda M: Dental complications of cytotoxic therapy in hodgkin’s disease-a case report. Br J Oral Surg 13:282, 1976

10. Hope-Simpson RE: The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Sot Med 58:9, 1965

11. HeIIgren L, Herslie K: A statistical and clinical study of herpes zoster. Geront CIin 8:70, 1966

12. NaIIy FF, Ross IH: Herpes zoster of the oral and facial structures. Oral Surg 32:221, 1971

13. Levin HL: Bacteriostasis and viroloav of hernetic lesions of the face and oral mucous membranes. Oral Surg 20:726. 1965

14. Bastian FO, et al: Herpes virus varicellae: isolated from human dorsal root ganglia. Arch Path01 97:331. 1974

15. Denny-Brown D, Adams RD, Fitzgerald PJ: Pathologic fea- tures of herpes zoster. Arch Neural Psychiat 51:216, 1944

16. Wildenhoff KE, Ipsen J, Esmann V, et al: Treatment of herpes zoster with ointment, including a multivariate analysis of symptoms and signs. Stand J Infect Dis 1 I : 1, 1979

17. Koramda FC, Dehmel EM, Kamm G, et al: Cutaneous com- plications in immunosuppressed renal homograft recip- ients. J Am Med Assoc 229~419, 1974

18. Dielert E: Zur Iinik des herpes zoster und zur pathogenise des symptomatischen zoster kranialer. Nerren Sch Mschr Zahnheilk 89: 135, 1979

19. Ferguson RH: Vasculitis associated with herpes zoster. Mayo Clin Proc 56:524, 1981