CHAPTER

22

ill Uncommon Inflammatory Conditions and Infections of the Orofacial Region,

Richard G. Topazian

This chapter discusses uncommon problems that are not presented elsewhere in this book or are of
sufficient importance to the practitioner to warrant additional emphasis.

PATHOGENIC FUNGI WITH MAXILLOFACIAL MANIFESTATIONS

Most fungi are saprophytes and rarely cause human disease. However, fungal diseases may occur when
defense mecha-nisms are compromised because of an underlying disease or the action of
immunosuppressive drugs. Prolonged antibiotic treatment, long-term steroid therapy, immunosuppres-
sive and antimetabolic drugs, immunodeficiency disease, chronic alcoholism, drug abuse, hemaropoietic
neoplasms, and diabetes may predispose an individual to fungal diseases. Fungal diseases also may
occur in apparently healthy individuals who have received a large or persistent inoculum. Of 100,000
species of fungi, approximately 20 are known to cause systemic infection, 20 are regularly isolated from
cutaneous infections, and 12 are associated with severe subcutaneous disease. Many opportunistic
species cause disease in patients who are medically compromised.

Among the diseases caused by pathogenic or opportunistic fungi are the systemic mycoses. Two
diseases caused by opportunistic fungi that are seen with increasing frequency are aspergillosis and
mucormycosis (zygomyco-sis, phycomycosis).

ASPERGILLOSIS

Aspergillosis is caused by members of the genus Aspergillus, a ubiquirous mold present in soil, decaying
vegetation, and all types of organic debris. Because its spores can be air-borne, it is a common
laboratory contaminant. Three species, Aspergillus fiinugutus, Aspergillus niger, and Aspergillus flavus,
account for most instances of human infections. It occurs in apparently healthy individuals, although in-
creasingly it is seen in patients who are immunocompro-mised or chronically debilitated, particularly
patients with cancer.

The disease is characterized by granulomatous inflam-mation with lesions of the skin, external ear, nasal
sinuses, orbit, eye, bronchi, lungs, and occasionally ocher organs, including the brain. Unlike other fungal
diseases, as-pergillosis often occurs without predisposing factors, al-though it can be seen in medically
compromised patients.

The three general categories of clinical aspergillosis are allergic, colonizing, and invasive. Invasive
aspergillosis may be disseminated and occurs most often in patients with an underlying disease such as
leukemia, lymphoma, or alco-holic cirrhosis, and in patients being treated with steroids, antibiotics, or
immunosuppressive or cytotoxic drugs. Dis-semination results from disruption of the normal flora, an
abnormal inflammatory response, lowered resistance caused by debilitating disease or drugs, and a
point of en-try for the fungus.

Nasoorbital (sinoorbital) aspergillosis is important to oral and maxillofacial surgeons and others
involved in the diagnosis and treatment of lesions in this region. The fun-gus may occur primarily in the
maxilla and orbit or may be derived from respiratory secretions in patients with pul-monary
aspergillosis. Sinusitis may allow this saprophytic organism to become sufficiently established to elicit a
granulomatous response.

Nasoorbital aspergillosis generally is characterized by an aspergilloma of the sinus chat may involve the
orbit and its contents and the brain. The presenting symptoms are sinusitis that has not responded to
conventional medical or surgical measures or sinusitis associated with swelling of the orbital soft tissues,
causing unilateral proptosis. A malodorous nasal discharge may be present, and the turbinates may be
swollen and gangrenous. Occasionally blindness occurs.

Figure 22-1 Aspergillosis manifested as a firm swelling of 3 years' duration in a 50-year-old farmer.
Radiographs showed opacity of the right maxillary sinus and bone destruction of the sinus walls. A chest
radiograph suggested pulmonary aspergillosis, but this could not be confirmed by biopsy because the
patient refused to have the procedure. Biopsy of the maxillary lesion was consistent with the diagnosis
of aspergillosis.

A review of 17 patients with paranasal aspergillosis showed 15 patients with proptosis, 8 with ethmoidal
mu-cosal swelling, 8 with maxillary mucosal swelling, and 2 with both ethmoidal and maxillary mucosal
swelling.31 En-ionasal granulomas and polyps were seldom present, and loss of vision occurred in
approximately 12% of the pa-:ients studied. The facial lesions typically were firm and )ainless, and the
duration of the disease ranged from 4 nonths to 10 years. A significant minority of patients with :hronic
invasive sinus aspergillosis have diabetes, use alco-)01 excessively, or have acquired immunodeficiency
syn-irome (AIDS)

Radiographically ethmoidal, antral, and ethinoido-mtral forms of aspergillosis are found (Figures 22-1
hrough 22-5), and bone may or may not be involved (sec 'igure 22-5). The differential diagnosis includes
suppura-ive sinusitis, malignancy of the sinus, and other types of ungal disease such as rhinocerebral
mucormycosis. Cul-ure of specimens produces the typical conidiophore and pore chains. Microscopic
examination of frozen paraffin ections of Aspergilius reveals hyphae 3 CO 12 j.Em thick with istinct cross
septa at intervals (Figures 22-6 and 22-7).10 .rlichman and Triegeri° described a facial form of as-
ergillosis in a patient receiving immunosuppressant rugs caused by A. fimigatus and characterized by
sub-iental space swelling and abscess formation. (See Chap-ns 3 and 11 for a detailed discussion of
culture and lentification techniques and a description of typical fun-d diseases.)
Figure 22-2 Lateral view of patient in Figure 22-1 shows swelling.

Figure 22-3 Left proptosis caused by advanced maxillary sinus aspergillosis. (From Mahgoub ES, Osman
AA: Primary as-pergilloma of paranasal sinuses in the Sudan: a review of seven-teen cases, BO Surg
56:132, 1969.)

Treatment The preferred treatment for aspergillosis ..onsists of surgical excision, adjunctive antifungal
therapy, and supportive care. If untreated, the disease is almost al-ways facal.1° As much of the lesion
should be removed as possible without damaging vital structures. The surgical opening should be large
enough to allow continued drainage. Accordingly, the Caldwell-Luc approach is used for maxillary sinus
disease to permit the wide removal of the medial antral wall. A radical etlimoidectomy is used when the
ethmoid sinuses are involved. Medicated packs nlaY be placed loosely in surgical defects for the initial
P°stoperative period, but they should be removed within Several days to permit drainage. Broad-
spectrum antifungal therapy alone is not effective for nasoorbital as-pergillosis. However, it is valuable
as an adjunct to surgery. Intravenous amphotericin 13 is the drug of choice for inva-sive disease;
however, when the lung or paranasal sinuses are affected, the drug is not effective as the sole therapy
but should he combined with surgery.' Plucytosine with amphotericin B is no more effective than
amphotericin B alone according to some studies." A combination of flucy-tosine and rifampin has been
used successfully in a patient with orbital aspergillosis." The prognosis for recovery is good, and cures
have been achieved with surgery alone. When amphotericin B is used, a daily dose of 0.8 to LS mg/kg
per day or up to double that dose given every other day fora minimum total dose of 2.5 to 3.0 g should
be ad-ministered to adult patients. This treatment extends for 6 to 8 weeks, and dose monitoring for
possible side effects is required." Amphotericin B therapy is described more fully subsequently.
Inhalation of a nystatin mist may be useful in the treatment of pulmonary aspergillosis.

figure 22-4 Right ethrnoidal aspergilloma with proptosis and haracteristic swelling of the medial canthal
region. (From Mah-oub ES, Osman AA: Primary aspergilloma of paranasal sinuses in he Sudan: a review
of seventeen cases, 8rf Surg 56:132, 1969 )

Figure 22-5 Opacity of the left maxillary sinus in a 55-year-old Homan with aspergillosis. (Courtesy S.
Roser, New York, NY.)

Figure 22-6 Biopsy of soft tissue mass shows segments of sep-tate lyphae consistent with aspergillosis,
some of which are cut at right angles so that they resemble spores. (X360, Gomori's methamine silver
stain.) (Courtesy S. Roser, New York, NY.)

Figure 22-7 High-power view of a granulomatous lesion com-posed of fibrous tissue infiltrated by
lymphocytes and giant cells containing elongated septate fungal filaments (arrows) that are consistent
with aspergillosis. (Periodic acid-Schiff stain.)

RHINOCEREBRAL MUCORMYCOSIS (ZYGOMYCOSIS, PHYCOMYCOSIS)

 Mucormycosis is an uncommon, acute fungal disease with a high mortality rate. It occurs in
rhinocerebral, pul-monary, cutaneous, gastrointestinal, central nervous sys-tem, and disseminated
forms.le," Rhinocerebral cormycosis is the type that most frequently involves the structures of the head.
The fungus is widespread and oc-curs in soil, in manure, on vegetables and fruits, and as bread mold. It
is a common laboratory contaminant. The disease in humans is caused by the genera Mutor, Rhizopus,
and Absidia rather than by Mucor alone.

The rhinocerebral form of the disease occurs predomi-nantly in dehydrated and acidotic patients,
particularly in patients with poorly controlled diabetes, patients with leukemia, and occasionally in
patients with kidney trans-plants.2425.34 It occurs in children who have become dehy-drated from
vomiting and diarrhea, in individuals with renal disease, in those undergoing dialysis, and in associa-tion
with corticosteroid or cytoroxic therapy in patients with hematological neoplasms.

The patient initially has signs and symptoms primarily in the intraoral, facial, orbital, paranasal sinus, or
cerebral regions. Symptoms referable to these areas in patients who are dehydrated and acidotic
warrant a high index of suspi-ion. Because of its lethal nature, rhinocerebral mucormy-:osis must be
recognized early and treated aggressively. Death can occur within several days of the onset of symp-
:oms even when appropriate treatment has been instituted.

Clinical Features In a comprehensive article, Schwartz it al." reviewed 99 cases. Among 70 patients,
palatal ul-:eration was present in 39%, facial swelling in 34%, facial iiscoloration in 20%, facial necrosis in
14%, nasal eschar ir ulceration in 47%, proptosis in 66%, periorbiral edema n 61%, and ptosis in 40%.
Eighty percent of the patients lad diabetes, and patient ages ranged from 2 months to '6 years (Figures
22-8 through 22-11). The disease can af-ect the mandible alone or the mandible and maxilla in the ame
patient.

Pillsbury and Fischer4° reviewed 13 cases and found fa-ial swelling, intranasal necrosis, lethargy, fever,
and ieadache in all patients. Decreased vision was present in 12%, dehydration in 85%, acidosis in 77%,
and facial nerve palsy in 77%. Other investigators have reported that the palate or alveolar process is
affected in 66% of patients. The prognosis is better when orbital signs are not present.'o The most
constant findings are facial pain and headache.

Figure 22-8 A, Necrotic area of the right palate and proven mu-cormycosis in a 48-year-old man with
kecoacidosis with fasting blood glucose level of 420 mg/100 Maxillary posterior teeth had been
extracted because of right facial pain of 18 months' du-ration. A sanguineous discharge from the right
nostril had been present for 1 month. Internal and external ophthalmoplegia was present with corneal
anesthesia but with no pupillary dilation. Right-sided ptosis was the most obvious sign of disease. B,
Paral-ysis of right lateral rectus muscle (cranial nerve VI) demonstrated when attempt was made to
direct the right eye laterally. (From Berger CL, Disque FC, Topazian RG: Rhinocerebral mucormyco-sis:
diagnosis and treatment, Oral Surg 40:27, 1975.)
Pathogenesis Mucormycosis probably is initiated in the susceptible individual by the inhalation of spores
into the nasal passages. The fungi invade arteries, causing throm-bosis with central extension, ischemia,
and dry gangrene of the affected structures. As the disease progresses from the nose to the orbit and
skull, the patient may become confused, obtunded, and comatose."-" Orbital signs and symptoms result
from vascular compromise of the orbital contents caused by thrombosis of the ethmoid arteries with
central extension through the sphenopalatine artery. When the apex of the orbit is affected, the
organisms ex-tend through the lateral wall of the cavernous sinus and involve the internal carotid artery
with resultant cerebral i ischemia and brain infarction.

figure 22-9 Characteristic necrotic area on the palate associated vith thrombosis of the sphenopalatine
artery. Necrosis of the lasal turbinates also may be seen in mucormycosis. (From Berger Disque FC,
Topazian RG: Rhinocerebral mucormycosis: diag-iosis and treatment, Oral Surg 40:27, 1975.)

Figure 22-10 Orbital cellulitis and ecchymosis of the right side f the face were prominent signs of
rhinocercbral mucormycosis n this 63-year-old patient with diabetes whose blood glucose level at
admission was 590 mg/100 ml and whose urinary acetone eve( was 3+. A maxillary third molar had been
extracted for facial oain 5 days earlier. The patient had been admitted to the hospi-:al because of
worsening facial pain but became comatose and died 1 day after admission despite intensive treatment.
Marked gangrenous necrosis was present on the right palate and alveolar process. (From Eilderton TE:
Fatal postextraction cerebral mu-cormycosis in an unknown diabetic,/ Oral Surg 32:297, 1974.)

Microscopically the fungus consists of wide, uneven, nonseptate, branching hyphae 6 to SO p.m wide
with long sporangiophores (Figures 22-12 and 22-13). It grows in 2 to 9 days on is agar and must be
distinguished from Aspergillus, which s smaller and seprate, with more acute branching than Rbizopus
and Mucor. Direct examina-tion and culture of scraping and biopsy specimens are nec-essary for
diagnosis.

Figure 22-11 Dilated and fixed right pupil and weakness of the right lateral rectus muscle in a 33-year-
old man with diabetic ke-toacidosis. Cranial nerves III, IV, V, and VI were affected. The right palate and
alveolar process showed signs of gangrenous necrosis. The patient developed left hemiplegia and
became comatose. He was :reared with insulin, amphotericin B, and antibiotics. After a prolonged
hospitalization, he recovered and subsequently was discharged. (From Tabachnick TT, Levine B:
Mucormycosis of the craniofacial structures, J Oral Surg 33:164, 1975.)

Figure 22-12 Microscopic appearance of mucormycosis, with long, broad, branching, nonseptate hyphae
with terminal globose sporangia.

Differential Diagnosis When the cerebral and orbital features predominate, the differential diagnosis
includes meningitis, superior orbital syndrome, cavernous sinus thrombosis, diabetic polyneuritis,
retrobulbar tumor, and recroorbital abscess. Other fungal diseases, particularly as-pergillosis, must be
distinguished from rhinocerebral mu-cormycosis because the sires and predisposing causes for both
diseases are similar. Necrosis and sloughing of facial soft tissues suggestive of noma rarely occur.
Figure 22-13 Sporangia of mucormycosis present in necrotic palatal tissue.

Paralysis of cranial nerves III, IV, and VI is common and causes external and internal ophthalmoplegia.
Cranial nerves V and VII are affected in approximately one third of cases, resulting in corneal anesthesia
and pupillary dila-tion. Loss of vision also may occur. The disease usually is unilateral. Orbital cellulitis
from ocher causes should be distinguished from mucormycosis (see Chapter 15).

On examination a fetid, purulosanguineous exudate commonly is seen on the nasal mucosa. The nasal
rurbi-nates become dark and necrotic. Palatal involvement be-gins as a unilateral, gray necrotic area
overlying the distri-bution of the sphenopalatine artery, particularly the anterior (greater) palatine
branch. The alveolar processes and the anterior maxilla also may become necrotic because of
nasopalatine artery involvement.

The nose is the most common site of initiation of this form of the disease and is associated with direct
extension to the paranasal sinuses, orbit, and cranial cavity. Odon-talgia and extraction of maxillary
teeth have been associ-ated with the onset of acute symptoms. Whether the toothache is the inciting
cause or the result of sinus dis-ease remains unclear. In some cases with orbital involve-ment, no clinical
evidence of sinus or nasal disease exists.

Treatment Early recognition of symptoms and institu-tion of vigorous surgical and medical therapy are
essential in the proper management of mucormycosis. Rapid cor-rection of dehydration and acidosis
and administration of insulin in patients with diabetes are required. Alternative treatment for the
primary disease should be considered in patients receiving antibiotics, immunosuppressive agents, or
antineoplastic drugs. Amphorericin B (Fungizone) is the antifungal agent of choice (daily dosage 1.0 to
1.5 mg/kg per day), although isolates may be resistant in vitro. Amphotericin B is fungistaric in patient
serum 48 hours after alternate-day doses of 1.0 mg/kg and can be given intl.: venously by one of several
regimens. Generally a total do: of 2 to 4 g should be given over 6 to 12 weeks. Administr i (ion of small
doses over a long interval minimizes toxicity and undesirable side effects.

Initially a test dose of 1 mg in 50 to 150 mL of 5% dez. trose in water is given intravenously over 20 to
30 minutes with careful monitoring for side effects, particularly chins fever, phlebitis, renal damage, and
anaphylaxis. On the sec_' ond day the patient is given 0.25 mg/kg in 500 mL of s% dextrose in water over
2 to 6 hours. The dose is increased daily in increments of 5 mg until the daily dose of 0.6 mg/kg is
achieved. If minor side effects such as headache, nausea, vomiting, and fever occur during the first few
days or weeks, the drug may be given on alternate days at a dose of 1.0 to 1.2 mg/kg. Although
creatinine clearance has been advocated as an excellent means of monitoring toxicity, if the blood urea
nitrogen level exceeds 40 mg/100 mL or the serum creatinine level exceeds 3.0 mg/100 mL, considera-
tion should be given to temporarily decreasing the dosage. Flucyrosine given with amphotericin B offers
no advantage over amphocericin B alone.

Surgical treatment to remove necrotic material and es-tablish drainage of all involved sinuses is
essential. Ac-cordingly, nasal septectomy, sphenoid sinusotomy, the Lynch operation (exposure of the
frotital sinus through the frontal sinus floor through the orbit), intranasal eth-moidectomy, Caldwell-Luc
operation with large nasal antrostomy, and partial palatectomy often are required (Figure 22-14).
Irrigation of the antrum with amphocericin B solutions has been advocated in the past but has not
proved effective. Orbital exenteration is necessary if vision has been lost.

Hyperbaric oxygen has been used as an adjunct to ag-gressive surgical debridement, amphocericin B,
and con-trol of the underlying predisposing conditions. Hyperbaric oxygen is fungistatic in vitro and
reduces tissue hypoxia and acidosis.

Prognosis Long-term survival ranges from 50 to 85% in patients treated with surgery and amphotericin
B. Variable recovery of cranial nerve function has been reported.

IN CASE REPORT

A 48-year-old man was admitted to a hospital medical ser-vice with severe pain and anesthesia of the
right side of the face. Eighteen months earlier the patient had severe toothaches in the maxillary right
quadrant. Extraction of the maxillary right premolars and first molar did not relieve the pain. Diabetes
mellitus had been diagnosed 1 year be-fore admission, and the patient was following an American
Diabetic Association diet and taking chlorpropamide (E"- abinese), 250 mg three times per day. Follow-
up was er-ratic because of poor cooperation by the patient. A bloody nasal discharge was noted 1
month before admission. me patient's physician started antibiotic and analgesic therapY. Over the next
several days the areas innervated by the right frontal, maxillary, and mandibular nerves exhibited pares-
thesia. During the week before admission, analgesics were less effective in controlling pain and the
patient was re-ferred to the hospital for treatment.

Figure 22-14 A, Result of partial palatectomy in a patient with mucormycosis. Organisms were found in
the sphenopalatine artery (see Figure 22-9). B, Site of palatectomy 2 years after surgery. The defect was
obturated initially by a complete denture and subsequently was closed surgically.

Examination revealed total right ophthalmoplegia, pto-sis, decreased vision of the right eye, and a
necrotic area of the hard palate (see Figures 22-8 and 22-9). The differen-tial diagnosis included
carcinoma of the palate, carcinoma of the maxillary antrum, and rhinocerebral mucormycosis.

The patient was admitted to the hospital with mild ke-toacidosis. Laboratory findings at admission
included he-moglobin, 13.2 g1100 mL; hematocrit, 42%; white blood cell count, 7500/mm3; and fasting
blood glucose concen-tration, 420 mg/100 mL. Radiographic examination re-vealed considerable
membrane thickening and an air-fluid level in the right maxillary antrum. Biopsy of the palatal ul-
ceration was performed, and a diagnosis of rhinocerebral mucormycosis was made (see Figure 22-13).

The patient received amphotericin B for 4 weeks. The dosage was increased until a daily dose of 1 mg/kg
was reached. Surgical therapy included excision of the necrotic area of the hard palate and a right partial
palatectomy. The surgical site healed well, and a prosthesis was inserted (see Figure 22-14, /3).
Figure 22-15 Follow-up photograph of patient in Figure 22-8, A 2 years after successful treatment of
mucormycosis with ampho-tericin B, control of diabetes, and partial palatectomy. Third cra-nial nerve
function had returned.

Figure 22-16 Persistent paralysis of the right lateral reccus mus-cle (cranial nerve VI) 2 years after
treatment of mucormycosis (see Figure 22.8, 8).

The patient was discharged 2 months after admission and was seen as an outpatient 1 year later. He was
in good health, and the diabetes was well controlled. The right eye ptosis resolved completely, but the
patient had not re-gained function of the ipsilateral fourth and sixth cranial nerves' (Figures 22-15 and
22-16).

Figure 22-17 A, Marked necrosis of the soft tissues of the upper lip and anterior maxilla in a 4-year-old
child with noma. Correction of the nutritional status and antibiotic therapy ar-rested the progression of
the disease. B, Facial deformity resulting from noma. The necrotic anterior portion of the maxilla
sloughed after 2 weeks of treatment producing the defect shown.

NOMA AND NOMALJKE LESIONS

noma, also known as gangrenous stomatitis and tantrum iris, is an acute, fulminating, toxic, progressive
gaff-;renous process of the oral and facial tissues that usually s seen in children who are debilitated and
poorly nour-shed. Early recognition, correction of predisposing fac-ors, and the use of antibiotics have
reduced the mortality tom a range of 75 to 90% in the preantibiotic era to ap-iroximately 10% today.

Noma usually occurs in the presence of malnutrition nd dehydration. Conditions favorable to the
development . if noma include famine, persistent poverty, prison camp ife, and epidemics of measles,
typhoid, and other febrile liseases. Noma has been described as a worldwide scourge vith a global
incidence of 140,000 cases.6 In developed ountries, however, a nomalike condition occurs in pa-ients
with blood dyscrasias or leukemias, and treatment s similar to that for classic noma. Although it has
been ecognized since antiquity, reports of the disease in the hiked States and in Europe first appeared in
the seven-eenth century.

CHARACTERISTICS OF NOMA :finical Features Noma is characterized by a rapid, pro-:ressive course

beginning as a small, painful, red spot or esicle on the attached gingiva in the premolar-molar region 1 f
the mandible. A necrotic ulcer rapidly forms and exposes inderlying bone. Stomatitis develops as the
lesion extends 'utward in a conelike fashion, causing painful cellulitis of the lips and cheeks. Marked
salivation, fetid odor, hyper-pyrexia, dehydration, leukocytosis, and a purulent oral dis-charge are
prominent. Overlying skin becomes inflamed, edematous, dark, and necrotic. Within a short period,
sloughing of soft tissues occurs, exposing underlying bone, teeth, and deeper soft tissues (Figures 22-17
and 22-18). Sec secondary hemorrhage is rare. The process may be arrested at xny stage, particularly if
treatment is instituted. If the pa-rocs general physical condition continues to deteriorate, death usually
results from pneumonia, septicemia, or persistent diarrhea.
Figure 22-18 Exposure of the left side of the mandible in an 8• year-old child with noma.

Tempest reviewed the causes of cancrum oris and noted that it is primarily a disease of children younger
than 10 years; 75% of cases occur in children between the ages of 2 and 5 years. Only 3 of 250 cases
occurred in adults. He confirmed that febrile diseases and malnutri-tion are important predisposing
factors. The most com-mon predisposing diseases, in descending order of fre-quency, are measles,
scarlet fever, typhoid, whooping sough, typhus, syphilis, tuberculosis, and leukemia. Kala-azar,
kwashiorkor, and magnesium deficiency also are con-deleted important predisposing factors.'

Associated gangrenous lesions in the anal region, scro-tum, scalp, umbilicus, and eyelids have been
noted in low-weight, ill, premature babies.2° Pseudomonas aeruginosa has xen cultured from these
lesions, and the disease has been :onsidered a result of P. aeruginosa septicemia. In a study Ghosal et
al..,2° all but 2 of 48 affected children died within 1 to 3 days after onset of the disease despite treat-
ment. The course of the disease was so rapid that the typi-:al slough often was absent.

Microbiology and Pathogenesis The fusospirochetal organisms Borrelia vincentii and Fusobacterium
nucleatum :Fusiformis fusiformis or Bacillus fusiformis) consistently are :ultured from noma lesions.
Prevotella melaninogenicus also may be present. Biopsy of tissue shows a mat of pre-dominantly gram-
negative, threadlike bacteria that can-lot be identified positively. Fusobacterium necrophorum, a
?athogen primarily associated with animal disease, may lave important causative and animal
transmission mplications.

Uohara and Knapps' suggested that a distinct pattern )f progression characterizes noma. It is initiated
by acute iecrotizing ulcerative gingivitis (ANUG) that leads to acute necrorizing ulcerative mucositis
(Vincent's angina). Jnder the influence of local and systemic factors, gan-;renous stomatitis,
agranulocytic ulcerations, and deep iecrotizing fusospirochetal infections eventually occur. Ar-:as of
gangrene result from vascular thrombosis, causing a :Pica] bluish or purple discoloration. Sloughing of
soft issues and exposure and devitalization of underlying bone and teeth ultimately occur.

Differential Diagnosis In its fully developed state, few diseases can be confused with cancrum oris. The
patient's 'Se, history of febrile illness, debilitated appearance, and :he presence of classic signs and
symptoms clearly indicate he diagnosis.

Treatment Treatment involves control of the underly-ng disease, correction of nutritional deficiencies,
estab-ishment of fluid and electrolyte balance, and administration of antibiotics. Penicillin is the drug of
choice and initially should be given intravenously in high doses. Blood transfusions may be-indicated in
children with se-vere anemia. Local irrigation with saline solution and gentle removal of necrotic debris
improve hygiene and speed resolution. Aggressive treatment with caustics, cautery, or wide excision
should be avoided. After the patient's defenses have been restored and assisted with antibiotics, the
inflammatory process regresses. Loose teeth and sequestra may be removed, but saucerization should
be avoided. A bed of granulation tissue develops beneath sequestra and permits subsequent healing by
secondary intention (Figure 22-19). If large orocu-taneous defects exist, fluid leakage may be controlled
initially by packing with saline solution-soaked or pe-troleum jelly gauze.

Figure 22-19 The anterior portion of the maxilla in a child with noma immediately after removal of the
loose bone segment. A bed of granulation tissue and a large nasal fistula are visible.

In the ensuing 3 to 6 months, significant quantities of scar tissue can develop that cause serious
deformity and require subsequent corrective surgery (Figure 22-20; see Figures 22-17, B; 22-18; and 22-
19). Major problems in-clude facial deformity, persistent saliva loss through oro-cutaneous fistulas,
trismus, facial asymmetry, and malde-velopment. Treatment of such deformities has been well
described by Adolph er al.' and Tempest47 and generally re-quires the use of local and distant flaps.
One-stage recon-struction has been especially useful when scheduling of multiple procedures is difficult.

True (intraarticular) ankylosis is uncommon after can-crum oris. In 229 cases of intraarticular ankylosis
of the mandible from a variety of causes, tantrum oris was not found as the cause in a single instance
reported by Topaz-ian.490 However, in another study, 3 of 22 patients did show true ankylosis of the
temporomandibular joint (TMJ) and other bone changes after cancrum ons.26 Although in-traarticular
ankylosis is infrequent, false or exrraarticular ankylosis is common and results from the scarring of the
soft tissues of the jaws (Figure 22-21). Correction of tris-mus by forceful opening brisemenr generally is
ineffective; however, excision of scar tissue between the jaws followed by grafting and possibly
coronoidectomy frequently is successful in rehabilitation of patients with noma-induced trismits.38

Figure 22-20 Sequelae of noma present a challenge for reconstruction.

Figure 22-21 Extraarticular ankylosis subsequent to scarring of noma.

Nomalike Lesions Individuals with compromised de-fenses are susceptible to a variety of infections,
includ-ing pathogenic fungal lesions. In adults, nomalike con-ditions have been associated with chronic
lymphatic leukemia, agranulocytosis, use of cytotoxic drugs, and systemic diseases such as kala-azar,
tuberculosis, leprosy, and syphilis.28 Nomalike lesions differ from true noma in that they usually occur in
adults rather than in chil-dren, the predisposing cause is not a febrile disease or malnutrition, the
inflammatory reaction in the sur-rounding soft tissues is absent, and the condition pro-gresses slowly.
The condition responds to correction of the underlying disease, antibiotic therapy, and improve-ment of
nutritional status. If feasible, discontinuation or reduction of the dosage of cytotoxic drugs and steroids
is helpful.

CAT-SCRATCH DISEASE Car-scratch disease is a self-limiting, benign illness charac-terized by malaise,

inflammation of solitary lymph nodes, low-grade fever, headache, and development of a papule at the
site of a cat bite or scratch, with regional lymph node involvement in approximately two thirds of
patients. The disease is caused by infection with organisms of the species Bartonella, nearly always
Bartonella henselae with occasional cases caused by Afipia fehs.'s Also known as benign lym-
phoreticulosis, benign inoculation lymphoreticulosis, and nonbacterial regional lymphadenitis, cat-
scratch disease Is common yet not generally reported because of its benign -se.
CARACTERISTICS

because cervical and preauricular nodes are enlarged in many patients, lymph node diseases should be
included in differential diagnosis. When an illness resembles cat-scratch disease but is atypical in certain
respects, the na- of the lymphadenopathy should be investigated fur .Arypical manifestations include
central nervous system disease, particularly encephalitis, erythema nodosum, thrombocytopenic
purpura, erythema annulare, ,ulovesicular eruptions, maculopapular rashes, and inaud's oculoglandular
disease. The differential diagnosis should include lymphogranuloma venereum, tu-mil, tuberculosis,
infectious mononucleosis, brucellosis, coccidioidomycosis, and other unilateral neck swellings. Criteria
necessary for diagnosis of cat-scratch deasase include lymphadenopathy, presence of an inoculation
site, absence of clinical and laboratory evidence of an-,er disease, and history of contact with a cat.

clinical Findings The characteristic finding of cat-scratch disease in a child or young adolescent is a single,
border lymph node in the region draining the site of a cat-scratch or bite that develops 2 to 8 weeks
after injury. The on at the site of inoculation persists for weeks after in-y. The enlarged node is variable
in size (Figure 22-22), i occasionally bilateral or generalized nodal disease may :ur. Multiple-node
involvement is believed to be the re-.t of a midline site or two separate sites of inoculation.9 .e nodes
are tender and tend to suppurate.

The order of frequency of nodal involvement is axillary,cervical , preauricular, submandibular,

epitrochlear, noral, inguinal, and subclavicular.29 Pain is not a prominennt feature, but a low-grade
fever, headache, and malaise usually are present. A history of contact with cats, particularly kittens, is
usually noted, and papule formation usually occurs from 3 to 30 days after inoculation. The inful node
develops approximately 2 weeks lacer. A flu like syndrome of fever, malaise, anorexia, headache, and
nrated temperature may be observed for several days. Patients with human immunodeficiency virus
may develop in lesions from which the cat-scratch bacillus has been demonstrated.

Because of concern for potential transmission of hepatitis viruses, human immunodeficiency virus, and
pil-ls even from well-screened sources, skin testing currently is not often used. Diagnosis is based on
clinical findings .

treatment and Prognosis Within 2 months the disease usually has run its course, as seen by an absence
of malaise and nodal regression. Recurrence of nodal tenderness has been reported for periods as long
as 2 years. Fluctuant nodes should be aspirated. Incision and drainage should be avoided because of the
possibility of fistula formation. If a large node persists, it should be removed to confirm a positive skin
test diagnosis or CO exclude malignant dis-ease. Antibiotics apparently do not affect the course of the
disease, although erythromycin or doxycycline have been used in treatment. In 15% of cases, atypical
pneumonia, acute encephalopathy sometimes terminating in death, and Parinaud's oculoglandular
syndrome occur.

Figure 22-22 A 14-year-old patient with a 4 X 5-cm, slightly ten-der mass in the left submental region.
One week before the onset of symptoms, his hand was scratched at home by one of numer-ous pet cats.
Because of a lack of other positive findings, he was tested with cat-scratch skin test antigen and had a
positive reac-tion. (From Gross BD, Case D: Cat-scratch disease, Oral Surg 43:698, 1977.)
Parinaud's Oculoglandular Syndrome Parinaud's ocu-loglandular syndrome is the most common ocular
mani-festation of cat-scratch fever. In 15% to 17% of patients with cat-scratch disease, unilateral
conjunctivitis with a single palpebral conjunctival polypoid granulomata is found with preauricular
lymphadenopathy.'°•" Preauricu-lar lymphadenopachy, conjunctivitis, and fever characterize this
disease. Patients are only mildly ill and generally com-pletely recover. The granulomatous area of the
conjunctiva commonly is polypoid in configuration, measures 0.5 to 2.0 cm in diameter, and has an
irregular nonerythemacous border (Figure 22-23).

Preauricular nodes invariably are affected, and 50% of patients have cervical node involvemenc.29 The
disease is self-limiting but may be treated with erythromycin or doxycycline with or without rifampin.7
The granuloma-taus lesions should not be surgically removed because they regress spontaneously.

Figure 22-23 A, Granulomatous lesion of the left conjunctiva in a 13-year-old girl with Parinaud's
oculoglandular syndrome and a 2-week history of low-grade fever, malaise, and anorexia. The patient
had regular and frequent contact with cats and dogs. B, Two tender preauricular nodes were present
that were rubbery in consistency and freely mobile. C, The dorsal surface of the hands demonstrated
numerous puncture and scratch marks. (From Loftus MJH, Sweeney G, Nemarich A, et al: Parinaud's
oculoglandular syndromej Ora/Sul 38:218, 1980.)

ERYSIPELAS: FACIAL LYMPHANGITIS

CHARACTERISTICS Erysipelas is a rapidly spreading, distinctive type of su-perficial cellulitis of the skin,
caused by streptococci, with prominent lymphatic involvement and with a predilection for the skin of
the face and scalp (Figure 22-24). On the face it is characterized by edema and erythema_ It should be
dis-tinguished from cellulitis caused by trauma, odontogenic infections, streptococcal pneumonia,
staphylococcal infec-tions, furunculosis, and atopic dermatitis. Erysipelas differs from cellulitis by its
raised, well-defined margins.37 On set usually is abrupt. Although uncommon, erysipelas should be
included in the differential diagnosis of acute fa' cial swelling.

The lesion generally affects infants, children, and the elderly. It is limited to the superficial layers of the
skin and is characteristically warm, tender, painful, indurated, and erythematous. The swelling is raised
with sharply deman cated borders and scalloped edges. It is distinctly pink to deep red and thereby
distinguishable from staphylococca, infections. Constitutional signs and symptoms include

figure 22-24 Erysipelas in a 2-year-old child. The lesion has a :haracteristic pink to deep red color, with
sharply demarcated and scalloped borders. (From Slade E, Danielson I', Goldberg M: Erysipelas: facial
lymphangitis, J Oral Surg 35:416, 1977.)

fever (104° F to 105° F) and regional lymphadenopathy. the lesion reaches its maximum extent by 3 to 5
days and leaves a desquamated surface after regression.

Erysipelas is caused by group A 13-hemolytic streptococci after bacterial invasion of facial abrasions,
lacerations, or punctures. Colonization of lymphatic channels produces diffuse lymphangitis. Erysipelas
also has been reported after tooth extraction.
treatment Before the discovery of antibiotics, the mortality rate for erysipelas was approximately 10%
to 20%, with death resulting from streptococcal septicemia, particularly in infants, the elderly, and the
debilitated. Currently treatment consists of the penicillin-resistant semisynthetic penicillins, nafcillin or
oxicillin (2.0 g q4h IV). if symptoms are not severe, doxycycline (SOO mg q61, PC)) or cefazolin (1.0 g q8h
IV) is recommended?' Antibiotic therapy usually results in a rapid resolution.

HAEMOPHILUS INFLUENZAE CELLULITIS

Haemaphilus influenzae cellulitis must be considered in the diferential diagnosis of any swelling of the
cheek or periorbital region, particularly in children between the ages of 8 months and 3 years, regardless
of sex. It typically appears as facial cellulitis in association with influenza, and its frequency is increasing.

Among 83 children with severe H. influenzae infection, 10% had facial cellulitis and 1% had orbital
cellulitis. H. influenzae cellulitis occasionally occurs after soft tissue injury of the cheek or face and
begins with a diffuse cellulitis that extends unilaterally from the mandible to the orbit (Figure 22-25); the
cellulitis is indurated, tender, and has a distinctive purple-blue or purple-red color. Symp-toms develop
slightly before or shortly after a short. febrile, nonspecific, upper respiratory tract infection. The white
blood cell count and temperature are elevated, and blood culture results usually are positive. H.
influenzae type commonly is cultured from blood or cellulitis aspirate. In-fection spreads by a
hematogenous route to the cheek from the nasopharynx, maxillary sinus, or middle ear. Some children
develop other septic foci (meningitis) be-cause of the accompanying bacteremia.

Figure 22-25 Marked cellulitis of the face in a 7-year-old boy whose blood cultures grew both H.
influenzae and streptococcal organisms of the viridans group. The color and distribution of the cellulitis
were typical of H. influenzae cellulitis.

IN CASE REPORT

A 7-year-old boy had facial cellulitis of odontogenic origin and a 1-week history of an upper respiratory
tract infection. No evidence of facial or cheek abrasion was present (Figure 22-25). H. influenzae and
streptococcal organisms of the viridans group were cultured from the cellulitis. Subsequent incision and
drainage, extraction of the involved tooth, and administration of parenteral and oral penicillin resulted
in rapid resolution of the condition. Although H. influenzae may have been a contaminant, the cellulitis
strongly re-sembled that of infantile H. influenzae.

An association between fl. influenzae cellulitis and ipsi-lateral otitis media has been reported. The
organism can be cultured from the ear, and involvement of the cheek can be explained by lymphatic
spread.'' This lesion must he dis-tinguished from the more common cellulitis of Streptococcus pyogenes,
which usually produces elevated borders and is uniformly red. It also must be distinguished from the
less common cellulicis caused by Streptoeocrus pneurnonke (Diplo-coccus pneumoniae), which also can
cause blue-purple cellulitis.

Treatment Because H. influenzae bacteremia may pro-gress to fatal meningitis and osteomyelitis, septic
arthritis, and epiglottitis, it should be treated vigorously. Ampicillin has been the drug of choice for the
treatment of H. influen-zae infections. Recently, however, an increasing number of H. influenzae type B
infections have been resistant to ampi-cillin. Therefore trimethoprim-sulfamethoxazole is rec-
ommended for upper respiratory tract infections and bronchitis; a variety of other antibiotics are
suggested as alternatives. For H. influenzae infection, meningitis, epiglot-tis, arthritis, and other serious
infections, cefotaxime (2.0 g q8h IV) plus gentamicin (2 mg/kg, first dose, then 1.7 mg/kg q8h) is
recommended as the drug of first choice.2'

INFECTIOUS ARTHRITIS OF THE TEMPOROMANDIBULAR JOINT

Arthritis of the TMJ may be traumatic, degenerative, rheumatoid, or infectious. Infectious arthritis is the
least common. It should be recognized and treated promptly to prevent destruction and consolidation
of the joint with subsequent ankylosis." In the growing individual, infec-tious arthritis of the joint affects
growth of the mandible and may result in hypoplasia of the involved side of the mandible with facial
asymmetry, micrognachia, and in-ability to open the mouth (Figure 22- 26).

Organisms may reach the joint by instrumentation, by laceration, through the bloodstream, by direct
extension, or by blunt trauma that predisposes the joint to infec-tion.'27'3' Almost any organism can
cause infectious arthri-tis, but it generally is caused by staphylococci, streptococci, and occasionally
gonococci. Infectious arthritis has been reported after pneumonia, gonorrhea, tuberculosis, syphilis,
meningitis, subacute bacterial endocarditis, sep-tic sore throat, scarlet fever, osteomyelitis, typhoid,
measles, infected wounds, peritonsillar abscess, otitis me-dia, mastoiditis, furunculosis, infected burns,
pyelicis, and sinusitis. Scarlet fever and typhoid fever may result in sep-ticemia that can affect any joint
and lead to otitis media or mastoiditis, which can involve the joint by direct exten-sion. In addition, TMJ
arthritis may result from direct ex-tension of temporal or condylar osteomyelitis or from soft tissue
abscesses.

Study of the causes of intraarticular (true) ankylosis of the TMJ showed that 25 (57%) of 44 patients and
87 (47%) of 185 patients, respectively, had infectious arthritis pre-ceding ankylosis."." Infectious arthritis
usually is suppu-rative, whereas that associated with scarlet fever, dysentery, and other acute febrile
illnesses is nonsuppurative. Clinical and Radiographic Findings Infectious arthri-tis is characterized by the
sudden onset of chills, fever, swelling over the joint, and tenderness of the joint to pal-pation.
Movement of the jaw is painful. Although early conventional radiographs may not disclose
abnormalities, destructive changes often are seen later. Early panographic or computed tomographic
images of the joint show sepa-ration of the articular surfaces caused by accumulation of fluid or pus.
Positive bone scan findings, although not specific for septic arthritis, suggest inflammation. These results
and clinical findings confirm joint involvement.

Figure 22-26 In this growing child, ankylosis resulted in hy-poplasia of the mandible on the right side and
inability to open the mouth because of fibrous or bony adheions of the condyle to the glenoid fossa
alone, or to the zygomatic arch and skull base. In this patient the right joint is affected with flatness of
the face on the left with deviation of the chin to the affected side as the mandible continues to grow on
the unaffected side.
Treatment Treatment is directed at overcoming the in-fection as early as possible to minimize joint
destruction and subsequent fibrous or bony ankylosis and other com-plications, such as temporal bone
osteomyelitis and in-tracranial abscesses.39 Whenever possible, antibiotic ther-apy should be based on
culture results. The joint should be aspirated under sterile conditions, and Gram stain per-formed.
Aerobic and anaerobic cultures should be ob-taMed for sensitivity testing. Empirical therapy should be-
gin immediately, directed at a broad spectrum of organisms because of the numerous potential sources
of infection; Distant loci of infection should be identified and treated.. Antibiotics recommended are
clindamycin (600 mg 11/4 every 6 hours), ampicillin-sulbactarn (Unasyn, 3 g ever! 6 hours). or cefazolin
(1.5 g every 6 hours). These dri. should be administered for 1 week followed by oral a. ministration for
an additional 3 weeks. When methaci.11a!, resistant S. aureus is suspected or cultured, vancomycln
recommended (15 mg/kg q12h IV; 125 mg q6h P0).

Formal incision and drainage seldom is necessary, but rated aspiration with 20- gauge needle is advised
until cultures are sterile. Arthroscopy has been used to confirm the diagnosis of suppurative arthritis of
the TMJ, for lavage oeh saline solution and antibiotic solutions, and for di-ra( monitoring of
convalescence."•3' Warrn preauricular soaks, analgesics, and adequate fluid and food intake arc
important supportive measures.

The patient should consume a liquid or soft diet in the early stages of the disease. Resting the joint is
desirable initially. After infection has subsided, joint function is encouraged to prevent ankylosis.