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Herpes zoster—A primary manifestation of chronic lymphatic leukemia
ORAL MEDICINE .
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HEBPES ZOSTEBclL PRIMARY YAN’IB’ESTATION OF CHRONIC LYMPHATIC LEUKEMIA Report of a Case Constuntine
H
P. Chmonas, D.D.S.,* Silver Spring, Md.
ZOSTER is the term assigned to the clinical manifestations resulting from irritation of a posterior root ganglion of a spinal nerve or an extramedullary ganglion of a cranial nerve. That disease is characterized by hurning. pruritus, acute neuralgio pain, and vesicular eruption in the a.rea of anatomic dist,ribution of the peripheral sensory nerves arising in the affected root gangli0n.l ERPES
ETIOLOGY
AND
INCIDENCE
Herpes zoster has been classified as primary and secondary in origin. It is thought that primary herpes zoster occurs directly as a result of infection of a posterior root ganglion.? Rosenow and Ofteda13 expressed t,heir belief that herpes zostcr resulted frotn hematogenous streptococcal infect,ion of a posterior root ganglion, McEwen4 and others feel that the virus of chickenpox. varicella, or a virus closely related to varieella is the causative agent in herp~~s zoster. Yerusal of the literature has not, revealed definitive substantiation for either theory. The viral theory, however, is strengthened by reports of the simultaneous occurrence of chickenpox and herpes zoster in the sam( household.5 Cecil and Loeb,2 in their Textbook of iliedicine, state: “Vari~lla has been produced experimentally in children by int,radermal inoculation with zoster vesicular fluid.” Secondary herpes zostcr has been reported t,o occur as a complication of debilitating diseases, such as pneumonia, tuberculosis, uremia, and nutritional drficiencics; as the result of trauma, such as fractures of the spine ikt~tl cranium and dislocations of the spine; frotn poisoning by carbon monosidc, arsenic, and bismuth; from irritation and/or impingement by neoplasms, subarachnoid hemorrhage, and cellular infiltrations (leukemias) : and as a *Formerly
Chief
Resident
in Oral
Surgery,
Millard
1429
Fillmore
Hospital.
Buffalo.
New
York
1430
CHACONAS
0,s.. O.M. 61 0.1’. December. 1960
complication of syphilis and meningitides.‘, ?, 8, i Decayed8 and supernumeraryl teeth have been said tu have a causal relationship, since in some instances pain and vesiculation have disappeared upon their removal. Incidence.-ln spite of the numerous etiological possibilities, herpes zoster is a relatively rare disease. It occurs more frequently in the male than in the fcmale,g and although it may occur at any age it is most common in the elderly.7 The disease apparently has a seasonal predisposition, since it occurs most often during cold, damp weather of early spring and late autumn.G The seasonal incidence and the age of the patients indicate a prevalence of the disease in persons who are overworked, fatigued, malnourished, or ill1
Site of Involvement.-Berggreen and Schiilerl” studied the sites of involvement in 2,014 cases of herpes zoster. The trigeminal nerve was involved in 16 per cent of the casts, the cervical nerves in 25 per cent, the dorsal spinal nerves in 48 per cent, the lumbar nerves in 9 per cent, and the sacral nerves in 2 per cent. Of the cranial nerves, the ophthalmic division of the trigeminal nerve was involved most frequently, followed by the maxillary and mandibuof the ophthalmic division of the lar divisions in the order named.l Uiction in cornea1 opacities as trigeminal nerve may affect the cornea, resulting Involvement of the maxillary or well as dermal lesions of the f0rehead.l mandibular divisions of the trigeminal nerve may result in lesions on the oral The most frequent intraoral mucosa and skin, or on both simultaneously.’ sites are the anterior portion of the tongue, the soft palate, and the cheek. Multiple involvement of the fifth, seventh, eighth, and ninth cranial nerves Involvement of the geniculate ganglion of the seventh cranial may occur.‘l nerve results in production of the so-called Ramsey-Hunt syndrome, which consists of herpes zoster, otic pain, vertigo, nausea, vomiting, gustatory disturbance, diminished hearing, and occasionally a bloody discharge from the is mediated through the external auditory meatusl! 6 The otic involvement ganglionic relationship to the eighth cranial nerve. Complete paralysis of the seventh and eighth cranial nerves may also occur. Symptoms and Gross Pathology.-Premonitory symptoms, both constitutional and local, precede the eruption of the vesiculation of herpes zostcr. Constitutional disorders, such as malaise, fever, headache, and dizziness, can occur prior t,o or concomitant with local symptoms of hyperthesia, itching, and a burning sensation.‘, ’ Involvement of one of the cranial nerves may also be indicated by facial muscle spasm.G Regional lymphadenopathy may bc present as a premonitory finding, or it may become apparent at the time of vesiculation.’ Following a short, variable period of premonitory symptoms, vesiculation occurs along the distribution of the peripheral terminations of the affected nerve or nerves.2 The vesicles develop upon a broad and slightly elevated erythematous base and are accompanied by neuralgic or acute, deep, burning The vesicles formed are filled with a clear serous fluid. Vesiculation pain.l is primarily unilateral, although cases of bilateral involvement have been reported.12 The vesicles persist for a variable time, depending upon extrinsic
Volume 13 Yumber
HERPES
ZOSTElt
1-w
12
I’actors of crlvironmcnt, clothing, sleeping hahits, and toilet CMT w ~~11 a~ intrinsic healing factors. Dermal vesicles may persist as long as tm (liLV% while those that occur in the oral cavity arc of short duration (hours). ‘l’ht! vesicles, when present in the oral cavity, arc similar and clinically indistil~Rupture of the oral vcsiclts guishablc from those found in herpes simplcs. leaves a lesion which is viewed as an eroded area within an erythematous riW. Ragged epithelial remnants of the ruptured vesicle walls are found attacht>tl at. the periphery of the eroded mucosa. Within several days the erosiou takcbs on a yellow-gray, cheesy coating which persists during repair of the nt>dt’l,lying mucosa.’ The pain that accompanies the oral lesions is at first of minor caonsequence. but when the vesicles rupture the pain becomes acute. ‘l’ht, onset of severe pain is thought to be due to exposure and irritation of t,hta t,rcldt*(l mucosa and nerve endings by saliva, air, food, bacteria, and subsequcLl\t SW ondary infection. The oral lesions of herpes zoster are of short,er dnratiotl than the dermal lcsions.l Residual scarring is infrrquent. E’evcr occurs concomitant with the onset of tlcrmal vesiculation, antI with its subsidence, usually within three to five days, drying or rupture Tut’that vesicles takes place.” Rupture of the dtrmal vesicle produces a hard, tlark. (*rustac(‘ous scab due to drying of the scrous n.1~1occasionally bloody disrhargts of the lesion. Secondary infection usually results at this time. Similar tcl other lesions affecting the skin, when the scab is lost thr rcpairctl lesion ~IYst>nts a white, ischemic, and fibrous appeaT.;\ncc. Pcrm&ncnt scarring of th(i skin ma>- occur following severe infection. but the ma;i&it~y of cases ~tr(~~c(~(i to a normal tissue appearance.” The pain accompanying dcrmal ItGons ix intense and deep-boring in nature, and it lUi\y persist after resolution ~,t’ this lt&nis.’ Histopathology.-111 herpes zoster, “as in herpes simplex, WC find cpithrli;l~ tlegenerations with the formation of vesicles beneath which there is a t~larkc~l inflatnmatory reaction. The eosinophilic bodies which occur in herpes simyl
REPORT
At the request of his physician, Mr. J. R., a GO-year-old Jr-hit.<; man, was seen on Oct. I, 1951, in the Oral Surgery Department of the Millard Fillmore Hospital in HuRalo, NW York.” His chief complaint was acute and constant oral and facial pain of approximatei> right days’ duration, accompanied by inability to eat, drink, sltvq), and pwform daily owl and facial hygienic measures comfortably. l G. G. Pritchard,
D.D.S.,
Chief
of Department.
CHACONAS Present Illness.-deven days previously, on Sept. 24, 1954, the patient was told upon his return home after obtaining a haircut, that the left side of his face presented multiple splotchy areas of redness. The patient was unaware of the condition but had noticed a feeling of warmth and itchiness on the left side of his face, which he attributed to his tonsorial care. Mirror examination confirmed the family’y observation, but the patient did not become alarmed. He was able to ingest his dinner without difficulty, but as the evening progressed he became increasingly uncomfortable. His family noticed that the facial splotches were undergoing a change. The patient was unable to describe them. Following a restless and uncomfortable night, blisters were observed the next morning on the left side of the patient’s face and on the tip of his tongue. His discomfort had increased greatly, and he was unable to shave or to take solid nourishment. Attempts to alleviate his discomfort with proprietary analgesics were only partially successful.
Fig. I.-Left
lateral
Note lesions extending view of dermal lesions (eighth day). and auriculotemporal nerve distribution.
into buccal
Later in the day (Sept. 25, 1954) the patient consulted a physician, who prescribed a salve for the facial lesions. Consideration was given to relief of pain and to dietary care. The patient took the prescription to a pharmacist friend, who quickly informed him that the salve would be of little value and promptly prescribed and dispensed his own remedy. The patient followed the pharmacist’s advice and took the medication without improvement or In fact, the pain and discomfort increased and the diet was painfully limited to relief. liquids. By the fifth day, the dermal vesiculations had ruptured and become “scabby. ” On the evening of the sixth day, the patient was seen by a general surgeon who found, in addition to the dermal and oral lesions, a tumefaction in the left maxillary vestibule in the premolar-molar region. Upon questioning by his physician, the patient revealed that his denture fit poorly and that it had been constructed by a dental technician friend without the benefit of attention by a licensed doctor of dentistry. Because of the tumefaction and oral lesions, the physician referred the patient to the Oral Surgery Department of the Millard Fillmore Hospital for consultation and diagnosis. Past history was noncontributory. The patient stated that he had been in good health until the present illness. F&dings.-The patient, when seen on Oct. 1, 1954, was in acute distress, moderately Malaise was prominent. cachectic, and dehydrated. Examination revealed multiple darkly
HERPES
ZOSTER
encrusted lesions on a broad erythematous base localized to the anatomic distribution of ulandibular division of the left trigeminal nerw. Facial lesions were present in the preauricular, paramandibular, and lateral inferior aspects of the cheek, in the inferiol and mental region to the midsagittal plane, and in tlw parietal wgion (Fig. 1 ). Thr les were srrondarily infected and varied in diameter t’ron~ II2 in(*h to 1 inch. Orally, tlllsrct \
Fig. 2.-Magnified
Fig. S.-Anterior
view
view
of labial
of dermal
and tongue lesions
and oral
lesions midline.
at eight
(eighth
days.
day)
Note
that
lt.si~.,ns stni
1
at
multiple aphthae with a cream-colored plaque center encircled in some instances with epitha rlixl The oral lesions were limited to the 1rt.t tags and in all instanws with an erythematous ring. side of the tip and anterior third of the tongue and to the cheek mucosa in its post+ srior The tongue was heavily coated in the middle and posterior thirds (Figs. 2 and 3 ‘I aspect. The patient stated that he had a maxillary denture but had If)een The maxilla was edentulous. An extensive granuloma fissuratum was pw srnt unable to use it since the onset of his illness.
CHACOKAS
OS..
O.hf.
di 0.1’.
December. 1960
The patient stated that the in the left maxillary vestibule in the cuspid-to-molar region. Five teeth, all periodontally in” had been present for a minimum of six months. “growth The patient was \vithout a mandibular prosthesis. volved, comprised the mandibular dentition. The oral tissues showed evitlcncc of dehydraSalivation was minimal, but thick and stringy. tion. submental, superficial, and superior deep cervical The left submaxillary, prcauricular, and supraclavicular lymph nodes were enlarged, nonmatted, and tender (Figs. 1 and 3). The The patient was questioned with regard lymph nodes on the right side were not remarkable. to eruptions elsewhere on his body and the possibility of a previous eruption. He denied the latter but stated that there was a rash on 11;s back at the time. The patient associated the rash with perspiration resulting from working in his yard during several days of hot weather approximately two days prior to the onset of his present illness. He stated that he perspired freely and was highly susceptible to heat-induced rashes. There was no evidence of vesieulation, but there was a red rash on his back, extending to the medial supraclavicular region in The axillary lymph nodes were not remarkable, an open V-neck manner.
Fig.
4.-Anterior
x’lew
of dermal
lesions onset followin of i,fn&;ay
treatment.
Twenty-three
Boentgenograms of the skull were ordered to rule out neoplastic impingement trigeminal nerve. The x-ray findings were reported to be within normal limits.
clays
after
upon the
Treatment.-The oral cavity was gently irrigated with warm water, and aqueous Merthiolate was applied to the oral lesions, The oral cavity was then irrigated with a warm solution of Maalox. The Maalox rinse brought comfort to the patient, and he was advised to Becotin with C three times daily was prescribed use it at home every two hours. Therapeutic as a dietary adjunct. A dietary regime was established to ensure adequate nourishment. Analgesics were not prescribed, since this had been done previously by the referring physician. A diagnosis of herpes zoster involving the mandibular branch of the left trigeminal nerve was made. The referring physician was contacted by telephone and given the diagnosis along with the recommendation that the patient be directed to a dermatologist for x-ray therapy. He agreed and the patient was referred to a dermatologist although he was to be followed at the oral surgery department as well.
HERPES
ZORTER
The diagnosis of herpes zoster was confirmed by the dermatologist on Oct. 3, 195-1. 11is of treatment follows: I‘ . . . He was given three x-ray treatments consisting of 100 roentgens filtered througll I mm. of aluminum with the factors of 100 kv. and 5 &Ma. to the preauricular ganglion on tht* on October 2, 3, and 8. At the time of his last left cheek, This dosage was administered t,xamination on October 35, the eruptions were subsiding satisfactorily, but Mr. J. B. still t:ontinued to have some residual pain in the area. He was returned to the care of his rcfvrriug physician and not seen after that time.“]*
report
During the period of x-ray treatment, the patient did not keep his appointments at tilt’ oral surgery clinic. Telephone conversations elicited the information that his oral and gc:ner:tl condition was improving. The patient was seen on Ocobtrr 15 after his visit to the dt~rm~t,ologist. The lesions were receding (twenty-three days since the onset of herpes zosttsr 1, :\lltl and preaurieular swelling was presenl he was “fairly comfortable. ” Gross left submaxillary but nonpaiuful (Fig. 4). A checkup appointment was made for the next week, but the patir,nt failed to keep this and other appointments during the following three months. On Jan. 15. 1955, the patient’s wife stated, during a telephone conversation, tlrat Mr. J. EC. was 110l eating well, was sleeping poorly, and had constant gastrointestinal discomfort,. An appointrevealed a gross13 ment was made and kept by the patient on Jan. 16. 1955. Examination apparrnt weight loss. The lesions of the herpes zoster were well healed, with lit,tle scarring. The granuloma fissuratum was reduced in size and in inflammatory response. The facial contour was within normal limits; however, examination of the lymph nodes of the brad ant1 The nodes were not matted or tendc,r. Thtneck revealed marked bilateral enlargement. nodes were grossly evident up011 patient was asked to remove his shirt, and the asillary palpation. There was no evidence of a dermal rash upon the back or chest. ‘IX> inguinal nodes were enlarged to the extent that t,hey were palpable through the patient’s trousers NS well as in the conventional manner. The patient leas immediately taken to the hematology laboratory for a complete blood count. On the basis of the cliniral findings and history. a diagnosis of leukemia was made. To be ruled out were Hodgkin’s disease, lymphosarc~omn. and infectious mononucleosis. The patient ‘Y referring physician was contacted by t,&yhour~ and advised of the recent findings and the tentat,irfs Iliagnosis. Thr results of thr ~:ompl~~t~~ blood couut done on January 38 were as follows : Red blood count White blood count FiIaments Bands Intermediate Ipmphocytes Prolymphocytes
4,770,ooo 370,000 2%
Hemoglobin 14.4 Gm. 99 per cent; 14.5 Gm. 100 per cent Platelets may be slightly decreased Occasional young lymphocytes Occasional small lymphocytes
Slight anisocytosis 85-90% Occasional smudge cells 5-S% -4 diagnosis of chronic lymphatic leukemia was made by the hospital hematologist. .i copy of the report was sent to the referring physician, and the case was discussed with him try telephone. The patient was then contacted and advised to see his physician for treatment. The patient was seen by the referring physician on Jan. 17, 1955, at which time hr was advised that he \yas seriously ill and required rst,onnive therapy. The patient, however, was not impressed and refused to undergo treatment. In view of this attitude, his physician told him that he had leukemia. Surprisingly, the patient atill refused treatment, saying that he had lived a good lengthy life and that he did not expect to live forever. At his family’s insistence, he finally agreed to undergo treatment at the Rosmell Park Memorial Institute, a cancer research and treatment center in Buffalo, New York. Treatment was instituted on Feb. 1, 1955. 9 treatment report dated June 22,1956, follows: consisted of steroid treatment and divided doses of . . . His first treatment triethylene mdamine for a total dosage of 25 mg. This therapy reduced the W.B.C. from 590,000 to 121,000. Since that time, he has had infrequent ingest&m of triethylene malamine and prednisone . . . which has reduced the size of the liver and spleen. From April 5, 1955, to April 19, 1955, he received irradiation therapy
CHACONAH
1436
to the spleen. Hc was last examined on June 7, 1956, at which time the blood findings were hemoglobin 11.2 Gm., W.B.C. 125,000, 96 per cent lymphocytes, platelets 88,000. He has been ingesting prednisone, 5 mg. twice daily, since about May 1.15 The patient was reported active and well in the fall of 1957. DISCUSSION
In the case just described herpes zoster was a primary symptom of As far as can be ascertained, this case is the first of its lymphatic leukemia. type reported in the dental literature and the thirty-eighth case of concurrent herpes zoster and leukemia reported in the general medical literature during the past sixty-seven years. Although herpes zoster is not common, Berggreen and Schiiler’P evaluation of 2,014 cases reveals a 40 per cent incidence in the head and neck region. The etiological factors, both local and systemic, previously listed in conjunction with the high relative percentage of herpes zoster in the head and neck area should give justification for the dentist to be aware of the ramifications as well as the primary aspects of the disease. Although the primary or “viral” form is most often seen, serious consideration and evaluation should be directed to the possibility tha,t the herpes zoster is secondary to systemic disorders or localized ganglionic and ncrvc irritations by Considerat,ion to the aforeinfectious agents, chemicals, tumors, and trauma. mentioned may prove lifesaving in some casts. In t,he case reported here a clinical diagnosis of herpes zostcr was made at the time of consultation, and he was returned to his referring physician The initial clinical examination of with a recommendation for x-ray therapy. the patient was directed primarily to a dctcrmination of the possibility of an infectious etiology or nerve irritation by tumefactions. The latter was ruled out by x-ray examination. The cause of the herpes zostclr was then assumed to be primary in origin, that is, infectious (viral). In ret,rospect, the “heat rash” observed upon the patient’s back and chest at the time of consultnt,ion was most likely an early transitory leukemid manifestation and thus should The rash, however, was not assigned have suggested systemic investigation. much importance in the illness, since the patient’s past history revealed multiWithout question, a complete: ple episodes in which a rash followed exertion. blood count taken at the time of consultation might have indicated the prescnce of leukemia, and thus antileukemic treatment could have been institutctl at that time. I am unable at this time to recall the reason that a complctr blood count was not included as part of the consultation. It should be pointed out that normally all patients examined in consult,ation at the department of oral surgery had a routine complete blood count and a urinalysis in addition to any specific test,s required. The delay in establishing the diagnosis of lenkemia was further complicated by the inability to get the pat,icnt to return for routine posttreatment checkups. Fortunately, some three months after the completion of x-ray therapy the patient was re-examined at the insistence Gross clinical symptoms suggestive of leukemia were present, of his family. and a complete blood study verified the clinical impression.
HERPES
1137
ZOSTER
This ease has been reported because of the interesting fact that oral and facial herpes zoster was t,he primary manifestation of a previously undiagnosed lymphatic leukemia and also to rciterat.e the necessity of routinely obtaining a complete blood count on every patient with a clisease of possible systemic origin. KFBFKFTC’ES . J 1
Oral Medicine, ed. 5. Philadelphia, 1946, J. B. Liypincott Company? 1. Burket. Lester w.: pp: 147, 151-153. A Text.book of Medicine, ed. 9, Philadelphia, 2. Cecil, Russell L., and Loeb, Robert F.: ‘1955, W. B. ‘Saunders Cbmpany, pp. 29, 30. and Experimental Production of Herpw 3. Rosenow, E. C., and Oftedal, S.: The Etiology Zoster, J. A. M. A. IX: 1968, 1915. 4. McEwen, F. L: The Association of Herpes Zoster With Varicella, Arch Dermat. & Syh. 2: 205, 1920. Conrurrent Herpes Zoster and Chic.kenpox, Arch. Int. 3. Feller, F., and Schnabel, T. F.: Med. 83: 502-504,1949. 6. Thoma, Eurt H.: Oral Pathology, ed. 3, St. Louis, 1950, The C. V. Mosby Company. pp. 1174-1176. 7. Wilson. S. A. K.. and Bruce. A. N.: Neurolozv.0. , cd. 2. Baltimore. 1955. Williams h: &lkins Comiany, p, 784.’ 8. Weinbereer. W.: Herpes zoster nach Zahnextraktion. Ztschr. f. stomatol. 31: 441. 1933. 9. Head, K: In AIlbut,a T. C., and Rolleston, H. (editors) : System of Medicinr, ntl. 2, London, 1910, Macmillan & Co., Ltd., pp. 7, 480. IO. Berggreen, P., and Schtier, E. G.: Zur Renntnis dcr r&alisation dcs Herpes zorter. Dermat. Wchnschr. 106: 216, 1938. 11. Dennis, F. L.: Herpes Zoster Oticus; a Case With Involvement of the 5th, 7th, 8th, and 9th Cranial Nerves With Complete Vcstibular Examination, Laryngoscope 35: 665: 19% 12. Campbe%,’ R. M.: Bilateral Herpes of the Trigeminal, Lnncet 1: 1066-1067, 1936. 13. Boyd, William: A Textbook of Pathology, ed. 5, Philadelphia, 1950, Lea & Fcbigcr, p. 908. 14. Hoak, Frank C.: Personal Communication. 15. Sheehan, George T,.: Personal Communication. -I
8605
CAMERON
ST.
I
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.
.
.
HEBPES ZOSTEBclL PRIMARY YAN’IB’ESTATION OF CHRONIC LYMPHATIC LEUKEMIA Report of a Case Constuntine
H
P. Chmonas, D.D.S.,* Silver Spring, Md.
ZOSTER is the term assigned to the clinical manifestations resulting from irritation of a posterior root ganglion of a spinal nerve or an extramedullary ganglion of a cranial nerve. That disease is characterized by hurning. pruritus, acute neuralgio pain, and vesicular eruption in the a.rea of anatomic dist,ribution of the peripheral sensory nerves arising in the affected root gangli0n.l ERPES
ETIOLOGY
AND
INCIDENCE
Herpes zoster has been classified as primary and secondary in origin. It is thought that primary herpes zoster occurs directly as a result of infection of a posterior root ganglion.? Rosenow and Ofteda13 expressed t,heir belief that herpes zostcr resulted frotn hematogenous streptococcal infect,ion of a posterior root ganglion, McEwen4 and others feel that the virus of chickenpox. varicella, or a virus closely related to varieella is the causative agent in herp~~s zoster. Yerusal of the literature has not, revealed definitive substantiation for either theory. The viral theory, however, is strengthened by reports of the simultaneous occurrence of chickenpox and herpes zoster in the sam( household.5 Cecil and Loeb,2 in their Textbook of iliedicine, state: “Vari~lla has been produced experimentally in children by int,radermal inoculation with zoster vesicular fluid.” Secondary herpes zostcr has been reported t,o occur as a complication of debilitating diseases, such as pneumonia, tuberculosis, uremia, and nutritional drficiencics; as the result of trauma, such as fractures of the spine ikt~tl cranium and dislocations of the spine; frotn poisoning by carbon monosidc, arsenic, and bismuth; from irritation and/or impingement by neoplasms, subarachnoid hemorrhage, and cellular infiltrations (leukemias) : and as a *Formerly
Chief
Resident
in Oral
Surgery,
Millard
1429
Fillmore
Hospital.
Buffalo.
New
York
1430
CHACONAS
0,s.. O.M. 61 0.1’. December. 1960
complication of syphilis and meningitides.‘, ?, 8, i Decayed8 and supernumeraryl teeth have been said tu have a causal relationship, since in some instances pain and vesiculation have disappeared upon their removal. Incidence.-ln spite of the numerous etiological possibilities, herpes zoster is a relatively rare disease. It occurs more frequently in the male than in the fcmale,g and although it may occur at any age it is most common in the elderly.7 The disease apparently has a seasonal predisposition, since it occurs most often during cold, damp weather of early spring and late autumn.G The seasonal incidence and the age of the patients indicate a prevalence of the disease in persons who are overworked, fatigued, malnourished, or ill1
Site of Involvement.-Berggreen and Schiilerl” studied the sites of involvement in 2,014 cases of herpes zoster. The trigeminal nerve was involved in 16 per cent of the casts, the cervical nerves in 25 per cent, the dorsal spinal nerves in 48 per cent, the lumbar nerves in 9 per cent, and the sacral nerves in 2 per cent. Of the cranial nerves, the ophthalmic division of the trigeminal nerve was involved most frequently, followed by the maxillary and mandibuof the ophthalmic division of the lar divisions in the order named.l Uiction in cornea1 opacities as trigeminal nerve may affect the cornea, resulting Involvement of the maxillary or well as dermal lesions of the f0rehead.l mandibular divisions of the trigeminal nerve may result in lesions on the oral The most frequent intraoral mucosa and skin, or on both simultaneously.’ sites are the anterior portion of the tongue, the soft palate, and the cheek. Multiple involvement of the fifth, seventh, eighth, and ninth cranial nerves Involvement of the geniculate ganglion of the seventh cranial may occur.‘l nerve results in production of the so-called Ramsey-Hunt syndrome, which consists of herpes zoster, otic pain, vertigo, nausea, vomiting, gustatory disturbance, diminished hearing, and occasionally a bloody discharge from the is mediated through the external auditory meatusl! 6 The otic involvement ganglionic relationship to the eighth cranial nerve. Complete paralysis of the seventh and eighth cranial nerves may also occur. Symptoms and Gross Pathology.-Premonitory symptoms, both constitutional and local, precede the eruption of the vesiculation of herpes zostcr. Constitutional disorders, such as malaise, fever, headache, and dizziness, can occur prior t,o or concomitant with local symptoms of hyperthesia, itching, and a burning sensation.‘, ’ Involvement of one of the cranial nerves may also be indicated by facial muscle spasm.G Regional lymphadenopathy may bc present as a premonitory finding, or it may become apparent at the time of vesiculation.’ Following a short, variable period of premonitory symptoms, vesiculation occurs along the distribution of the peripheral terminations of the affected nerve or nerves.2 The vesicles develop upon a broad and slightly elevated erythematous base and are accompanied by neuralgic or acute, deep, burning The vesicles formed are filled with a clear serous fluid. Vesiculation pain.l is primarily unilateral, although cases of bilateral involvement have been reported.12 The vesicles persist for a variable time, depending upon extrinsic
Volume 13 Yumber
HERPES
ZOSTElt
1-w
12
I’actors of crlvironmcnt, clothing, sleeping hahits, and toilet CMT w ~~11 a~ intrinsic healing factors. Dermal vesicles may persist as long as tm (liLV% while those that occur in the oral cavity arc of short duration (hours). ‘l’ht! vesicles, when present in the oral cavity, arc similar and clinically indistil~Rupture of the oral vcsiclts guishablc from those found in herpes simplcs. leaves a lesion which is viewed as an eroded area within an erythematous riW. Ragged epithelial remnants of the ruptured vesicle walls are found attacht>tl at. the periphery of the eroded mucosa. Within several days the erosiou takcbs on a yellow-gray, cheesy coating which persists during repair of the nt>dt’l,lying mucosa.’ The pain that accompanies the oral lesions is at first of minor caonsequence. but when the vesicles rupture the pain becomes acute. ‘l’ht, onset of severe pain is thought to be due to exposure and irritation of t,hta t,rcldt*(l mucosa and nerve endings by saliva, air, food, bacteria, and subsequcLl\t SW ondary infection. The oral lesions of herpes zoster are of short,er dnratiotl than the dermal lcsions.l Residual scarring is infrrquent. E’evcr occurs concomitant with the onset of tlcrmal vesiculation, antI with its subsidence, usually within three to five days, drying or rupture Tut’that vesicles takes place.” Rupture of the dtrmal vesicle produces a hard, tlark. (*rustac(‘ous scab due to drying of the scrous n.1~1occasionally bloody disrhargts of the lesion. Secondary infection usually results at this time. Similar tcl other lesions affecting the skin, when the scab is lost thr rcpairctl lesion ~IYst>nts a white, ischemic, and fibrous appeaT.;\ncc. Pcrm&ncnt scarring of th(i skin ma>- occur following severe infection. but the ma;i&it~y of cases ~tr(~~c(~(i to a normal tissue appearance.” The pain accompanying dcrmal ItGons ix intense and deep-boring in nature, and it lUi\y persist after resolution ~,t’ this lt&nis.’ Histopathology.-111 herpes zoster, “as in herpes simplex, WC find cpithrli;l~ tlegenerations with the formation of vesicles beneath which there is a t~larkc~l inflatnmatory reaction. The eosinophilic bodies which occur in herpes simyl
REPORT
At the request of his physician, Mr. J. R., a GO-year-old Jr-hit.<; man, was seen on Oct. I, 1951, in the Oral Surgery Department of the Millard Fillmore Hospital in HuRalo, NW York.” His chief complaint was acute and constant oral and facial pain of approximatei> right days’ duration, accompanied by inability to eat, drink, sltvq), and pwform daily owl and facial hygienic measures comfortably. l G. G. Pritchard,
D.D.S.,
Chief
of Department.
CHACONAS Present Illness.-deven days previously, on Sept. 24, 1954, the patient was told upon his return home after obtaining a haircut, that the left side of his face presented multiple splotchy areas of redness. The patient was unaware of the condition but had noticed a feeling of warmth and itchiness on the left side of his face, which he attributed to his tonsorial care. Mirror examination confirmed the family’y observation, but the patient did not become alarmed. He was able to ingest his dinner without difficulty, but as the evening progressed he became increasingly uncomfortable. His family noticed that the facial splotches were undergoing a change. The patient was unable to describe them. Following a restless and uncomfortable night, blisters were observed the next morning on the left side of the patient’s face and on the tip of his tongue. His discomfort had increased greatly, and he was unable to shave or to take solid nourishment. Attempts to alleviate his discomfort with proprietary analgesics were only partially successful.
Fig. I.-Left
lateral
Note lesions extending view of dermal lesions (eighth day). and auriculotemporal nerve distribution.
into buccal
Later in the day (Sept. 25, 1954) the patient consulted a physician, who prescribed a salve for the facial lesions. Consideration was given to relief of pain and to dietary care. The patient took the prescription to a pharmacist friend, who quickly informed him that the salve would be of little value and promptly prescribed and dispensed his own remedy. The patient followed the pharmacist’s advice and took the medication without improvement or In fact, the pain and discomfort increased and the diet was painfully limited to relief. liquids. By the fifth day, the dermal vesiculations had ruptured and become “scabby. ” On the evening of the sixth day, the patient was seen by a general surgeon who found, in addition to the dermal and oral lesions, a tumefaction in the left maxillary vestibule in the premolar-molar region. Upon questioning by his physician, the patient revealed that his denture fit poorly and that it had been constructed by a dental technician friend without the benefit of attention by a licensed doctor of dentistry. Because of the tumefaction and oral lesions, the physician referred the patient to the Oral Surgery Department of the Millard Fillmore Hospital for consultation and diagnosis. Past history was noncontributory. The patient stated that he had been in good health until the present illness. F&dings.-The patient, when seen on Oct. 1, 1954, was in acute distress, moderately Malaise was prominent. cachectic, and dehydrated. Examination revealed multiple darkly
HERPES
ZOSTER
encrusted lesions on a broad erythematous base localized to the anatomic distribution of ulandibular division of the left trigeminal nerw. Facial lesions were present in the preauricular, paramandibular, and lateral inferior aspects of the cheek, in the inferiol and mental region to the midsagittal plane, and in tlw parietal wgion (Fig. 1 ). Thr les were srrondarily infected and varied in diameter t’ron~ II2 in(*h to 1 inch. Orally, tlllsrct \
Fig. 2.-Magnified
Fig. S.-Anterior
view
view
of labial
of dermal
and tongue lesions
and oral
lesions midline.
at eight
(eighth
days.
day)
Note
that
lt.si~.,ns stni
1
at
multiple aphthae with a cream-colored plaque center encircled in some instances with epitha rlixl The oral lesions were limited to the 1rt.t tags and in all instanws with an erythematous ring. side of the tip and anterior third of the tongue and to the cheek mucosa in its post+ srior The tongue was heavily coated in the middle and posterior thirds (Figs. 2 and 3 ‘I aspect. The patient stated that he had a maxillary denture but had If)een The maxilla was edentulous. An extensive granuloma fissuratum was pw srnt unable to use it since the onset of his illness.
CHACOKAS
OS..
O.hf.
di 0.1’.
December. 1960
The patient stated that the in the left maxillary vestibule in the cuspid-to-molar region. Five teeth, all periodontally in” had been present for a minimum of six months. “growth The patient was \vithout a mandibular prosthesis. volved, comprised the mandibular dentition. The oral tissues showed evitlcncc of dehydraSalivation was minimal, but thick and stringy. tion. submental, superficial, and superior deep cervical The left submaxillary, prcauricular, and supraclavicular lymph nodes were enlarged, nonmatted, and tender (Figs. 1 and 3). The The patient was questioned with regard lymph nodes on the right side were not remarkable. to eruptions elsewhere on his body and the possibility of a previous eruption. He denied the latter but stated that there was a rash on 11;s back at the time. The patient associated the rash with perspiration resulting from working in his yard during several days of hot weather approximately two days prior to the onset of his present illness. He stated that he perspired freely and was highly susceptible to heat-induced rashes. There was no evidence of vesieulation, but there was a red rash on his back, extending to the medial supraclavicular region in The axillary lymph nodes were not remarkable, an open V-neck manner.
Fig.
4.-Anterior
x’lew
of dermal
lesions onset followin of i,fn&;ay
treatment.
Twenty-three
Boentgenograms of the skull were ordered to rule out neoplastic impingement trigeminal nerve. The x-ray findings were reported to be within normal limits.
clays
after
upon the
Treatment.-The oral cavity was gently irrigated with warm water, and aqueous Merthiolate was applied to the oral lesions, The oral cavity was then irrigated with a warm solution of Maalox. The Maalox rinse brought comfort to the patient, and he was advised to Becotin with C three times daily was prescribed use it at home every two hours. Therapeutic as a dietary adjunct. A dietary regime was established to ensure adequate nourishment. Analgesics were not prescribed, since this had been done previously by the referring physician. A diagnosis of herpes zoster involving the mandibular branch of the left trigeminal nerve was made. The referring physician was contacted by telephone and given the diagnosis along with the recommendation that the patient be directed to a dermatologist for x-ray therapy. He agreed and the patient was referred to a dermatologist although he was to be followed at the oral surgery department as well.
HERPES
ZORTER
The diagnosis of herpes zoster was confirmed by the dermatologist on Oct. 3, 195-1. 11is of treatment follows: I‘ . . . He was given three x-ray treatments consisting of 100 roentgens filtered througll I mm. of aluminum with the factors of 100 kv. and 5 &Ma. to the preauricular ganglion on tht* on October 2, 3, and 8. At the time of his last left cheek, This dosage was administered t,xamination on October 35, the eruptions were subsiding satisfactorily, but Mr. J. B. still t:ontinued to have some residual pain in the area. He was returned to the care of his rcfvrriug physician and not seen after that time.“]*
report
During the period of x-ray treatment, the patient did not keep his appointments at tilt’ oral surgery clinic. Telephone conversations elicited the information that his oral and gc:ner:tl condition was improving. The patient was seen on Ocobtrr 15 after his visit to the dt~rm~t,ologist. The lesions were receding (twenty-three days since the onset of herpes zosttsr 1, :\lltl and preaurieular swelling was presenl he was “fairly comfortable. ” Gross left submaxillary but nonpaiuful (Fig. 4). A checkup appointment was made for the next week, but the patir,nt failed to keep this and other appointments during the following three months. On Jan. 15. 1955, the patient’s wife stated, during a telephone conversation, tlrat Mr. J. EC. was 110l eating well, was sleeping poorly, and had constant gastrointestinal discomfort,. An appointrevealed a gross13 ment was made and kept by the patient on Jan. 16. 1955. Examination apparrnt weight loss. The lesions of the herpes zoster were well healed, with lit,tle scarring. The granuloma fissuratum was reduced in size and in inflammatory response. The facial contour was within normal limits; however, examination of the lymph nodes of the brad ant1 The nodes were not matted or tendc,r. Thtneck revealed marked bilateral enlargement. nodes were grossly evident up011 patient was asked to remove his shirt, and the asillary palpation. There was no evidence of a dermal rash upon the back or chest. ‘IX> inguinal nodes were enlarged to the extent that t,hey were palpable through the patient’s trousers NS well as in the conventional manner. The patient leas immediately taken to the hematology laboratory for a complete blood count. On the basis of the cliniral findings and history. a diagnosis of leukemia was made. To be ruled out were Hodgkin’s disease, lymphosarc~omn. and infectious mononucleosis. The patient ‘Y referring physician was contacted by t,&yhour~ and advised of the recent findings and the tentat,irfs Iliagnosis. Thr results of thr ~:ompl~~t~~ blood couut done on January 38 were as follows : Red blood count White blood count FiIaments Bands Intermediate Ipmphocytes Prolymphocytes
4,770,ooo 370,000 2%
Hemoglobin 14.4 Gm. 99 per cent; 14.5 Gm. 100 per cent Platelets may be slightly decreased Occasional young lymphocytes Occasional small lymphocytes
Slight anisocytosis 85-90% Occasional smudge cells 5-S% -4 diagnosis of chronic lymphatic leukemia was made by the hospital hematologist. .i copy of the report was sent to the referring physician, and the case was discussed with him try telephone. The patient was then contacted and advised to see his physician for treatment. The patient was seen by the referring physician on Jan. 17, 1955, at which time hr was advised that he \yas seriously ill and required rst,onnive therapy. The patient, however, was not impressed and refused to undergo treatment. In view of this attitude, his physician told him that he had leukemia. Surprisingly, the patient atill refused treatment, saying that he had lived a good lengthy life and that he did not expect to live forever. At his family’s insistence, he finally agreed to undergo treatment at the Rosmell Park Memorial Institute, a cancer research and treatment center in Buffalo, New York. Treatment was instituted on Feb. 1, 1955. 9 treatment report dated June 22,1956, follows: consisted of steroid treatment and divided doses of . . . His first treatment triethylene mdamine for a total dosage of 25 mg. This therapy reduced the W.B.C. from 590,000 to 121,000. Since that time, he has had infrequent ingest&m of triethylene malamine and prednisone . . . which has reduced the size of the liver and spleen. From April 5, 1955, to April 19, 1955, he received irradiation therapy
CHACONAH
1436
to the spleen. Hc was last examined on June 7, 1956, at which time the blood findings were hemoglobin 11.2 Gm., W.B.C. 125,000, 96 per cent lymphocytes, platelets 88,000. He has been ingesting prednisone, 5 mg. twice daily, since about May 1.15 The patient was reported active and well in the fall of 1957. DISCUSSION
In the case just described herpes zoster was a primary symptom of As far as can be ascertained, this case is the first of its lymphatic leukemia. type reported in the dental literature and the thirty-eighth case of concurrent herpes zoster and leukemia reported in the general medical literature during the past sixty-seven years. Although herpes zoster is not common, Berggreen and Schiiler’P evaluation of 2,014 cases reveals a 40 per cent incidence in the head and neck region. The etiological factors, both local and systemic, previously listed in conjunction with the high relative percentage of herpes zoster in the head and neck area should give justification for the dentist to be aware of the ramifications as well as the primary aspects of the disease. Although the primary or “viral” form is most often seen, serious consideration and evaluation should be directed to the possibility tha,t the herpes zoster is secondary to systemic disorders or localized ganglionic and ncrvc irritations by Considerat,ion to the aforeinfectious agents, chemicals, tumors, and trauma. mentioned may prove lifesaving in some casts. In t,he case reported here a clinical diagnosis of herpes zostcr was made at the time of consultation, and he was returned to his referring physician The initial clinical examination of with a recommendation for x-ray therapy. the patient was directed primarily to a dctcrmination of the possibility of an infectious etiology or nerve irritation by tumefactions. The latter was ruled out by x-ray examination. The cause of the herpes zostclr was then assumed to be primary in origin, that is, infectious (viral). In ret,rospect, the “heat rash” observed upon the patient’s back and chest at the time of consultnt,ion was most likely an early transitory leukemid manifestation and thus should The rash, however, was not assigned have suggested systemic investigation. much importance in the illness, since the patient’s past history revealed multiWithout question, a complete: ple episodes in which a rash followed exertion. blood count taken at the time of consultation might have indicated the prescnce of leukemia, and thus antileukemic treatment could have been institutctl at that time. I am unable at this time to recall the reason that a complctr blood count was not included as part of the consultation. It should be pointed out that normally all patients examined in consult,ation at the department of oral surgery had a routine complete blood count and a urinalysis in addition to any specific test,s required. The delay in establishing the diagnosis of lenkemia was further complicated by the inability to get the pat,icnt to return for routine posttreatment checkups. Fortunately, some three months after the completion of x-ray therapy the patient was re-examined at the insistence Gross clinical symptoms suggestive of leukemia were present, of his family. and a complete blood study verified the clinical impression.
HERPES
1137
ZOSTER
This ease has been reported because of the interesting fact that oral and facial herpes zoster was t,he primary manifestation of a previously undiagnosed lymphatic leukemia and also to rciterat.e the necessity of routinely obtaining a complete blood count on every patient with a clisease of possible systemic origin. KFBFKFTC’ES . J 1
Oral Medicine, ed. 5. Philadelphia, 1946, J. B. Liypincott Company? 1. Burket. Lester w.: pp: 147, 151-153. A Text.book of Medicine, ed. 9, Philadelphia, 2. Cecil, Russell L., and Loeb, Robert F.: ‘1955, W. B. ‘Saunders Cbmpany, pp. 29, 30. and Experimental Production of Herpw 3. Rosenow, E. C., and Oftedal, S.: The Etiology Zoster, J. A. M. A. IX: 1968, 1915. 4. McEwen, F. L: The Association of Herpes Zoster With Varicella, Arch Dermat. & Syh. 2: 205, 1920. Conrurrent Herpes Zoster and Chic.kenpox, Arch. Int. 3. Feller, F., and Schnabel, T. F.: Med. 83: 502-504,1949. 6. Thoma, Eurt H.: Oral Pathology, ed. 3, St. Louis, 1950, The C. V. Mosby Company. pp. 1174-1176. 7. Wilson. S. A. K.. and Bruce. A. N.: Neurolozv.0. , cd. 2. Baltimore. 1955. Williams h: &lkins Comiany, p, 784.’ 8. Weinbereer. W.: Herpes zoster nach Zahnextraktion. Ztschr. f. stomatol. 31: 441. 1933. 9. Head, K: In AIlbut,a T. C., and Rolleston, H. (editors) : System of Medicinr, ntl. 2, London, 1910, Macmillan & Co., Ltd., pp. 7, 480. IO. Berggreen, P., and Schtier, E. G.: Zur Renntnis dcr r&alisation dcs Herpes zorter. Dermat. Wchnschr. 106: 216, 1938. 11. Dennis, F. L.: Herpes Zoster Oticus; a Case With Involvement of the 5th, 7th, 8th, and 9th Cranial Nerves With Complete Vcstibular Examination, Laryngoscope 35: 665: 19% 12. Campbe%,’ R. M.: Bilateral Herpes of the Trigeminal, Lnncet 1: 1066-1067, 1936. 13. Boyd, William: A Textbook of Pathology, ed. 5, Philadelphia, 1950, Lea & Fcbigcr, p. 908. 14. Hoak, Frank C.: Personal Communication. 15. Sheehan, George T,.: Personal Communication. -I
8605
CAMERON
ST.
I