Bacterial Infections

CLINICAL FEATURES: Nonbullous impetigo (impetigo contagiosa) is the more prevalent pattern and occurs most frequently on the legs, with less common involvement noted on the trunk, scalp, or face. The facial lesions usually develop around the nose and mouth. In many patients with facial involvement, the pathogenic bacteria are harbored in the nose and spread onto the skin into previously damaged sites such as scratches or abrasions. Often, facial lesions will have a linear pattern that corresponds to previous fingernail scratches. The infection is more prevalent in school-aged children but also may be seen in adults. The peak occurrence is during the summer or early fall in hot, moist climates. Impetigo is contagious and easily spread in crowded or unsanitary living conditions.

Nonbullous impetigo initially appears as red macules or papules, with the subsequent development of fragile vesicles. These vesicles quickly rupture and become covered with a thick, amber crust (Fig. 5-1). The crusts are adherent and have been described as “cornflakes glued to the surface.” Some cases may be confused with exfoliative cheilitis (see page 304) or recurrent herpes simplex (see page 243). Pruritus is common, and scratching often causes the lesions to spread (Fig. 5-2). Lymphangitis, cellulitis, fever, anorexia, and malaise are uncommon, although leukocytosis occurs in about half of affected patients.

Bullous impetigo usually is caused by S. aureus and also has been termed staphylococcal impetigo. Like the nonbullous form, it most frequently affects the extremities, trunk, and face. Infants and newborns are infected most commonly, but the disease also may occur in children and adults. The lesions are characterized by superficial vesicles that rapidly enlarge to form larger flaccid bullae. Initially, the bullae are filled with clear serous fluid, but the contents of the bullae quickly become more turbid and eventually purulent. Although the bullae may remain intact, they usually rupture and develop a thin brown crust that some describe as “lacquer.” Weakness, fever, and diarrhea may be seen. Lymphadenopathy and cellulitis are unusual complications. Meningitis and pneumonia are very rare but may lead to serious complications, even death.

DIAGNOSIS: A strong presumptive diagnosis can normally be made from the clinical presentation. When the diagnosis is not obvious clinically or the infection fails to respond to standard therapy within 7 days, the definitive diagnosis requires isolation of S. pyogenes or S. aureus from cultures of involved skin.

TREATMENT AND PROGNOSIS: For patients with nonbullous impetigo involving only a small area with few lesions, topical mupirocin has been shown to be effective. Fusidic acid (available in Europe, not in the United States) also has been very effective; however, increasing reports of resistance are diminishing its use. Removal of the crusts with a clean cloth soaked in warm soapy water is recommended before application of topical therapy, rather than placing the medication on inert, dried, exfoliating skin. For bullous or more extensive lesions, topical antibiotic drugs often are insufficient; the treatment of choice is a 1-week course of a systemic oral antibiotic. The best antibiotic is one that is effective against both S. pyogenes and penicillin-resistant S. aureus. Cephalexin, trimethoprim-sulfamethoxazole, dicloxacillin, flucloxacillin, and amoxicillin-clavulanic acid represent good current choices. Erythromycin or clindamycin can be used in patients sensitive to penicillin, but resistance by S. aureus to erythromycin has become an increasing problem. If left untreated, then the lesions often enlarge slowly and spread. Serious complications, such as acute glomerulonephritis, are rare but possible in prolonged cases. Inappropriate diagnosis and treatment with topical corticosteroids may produce resolution of the surface crusts, but infectious, red, raw lesions remain.

CLINICAL FEATURES: Erysipelas tends to occur primarily in young and older adult patients or in those who are debilitated, diabetic, immunosuppressed, obese, or alcoholic. Patients who have areas of chronic lymphedema or large surgical scars (such as postmastectomy or saphenous venectomy) also are susceptible to this disease. The infection may occur anywhere on the skin, especially in areas of previous trauma. The most commonly affected site is the leg in areas affected by tinea pedis (athlete’s foot). The face, arm, and upper thigh also frequently are infected. In facial erysipelas, an increased prevalence is noted in the winter and spring months, whereas summer is the peak period of involvement of the lower extremities.

When lesions occur on the face, they normally appear on the cheeks, eyelids, and bridge of the nose, at times producing a butterfly-shaped lesion that may resemble lupus erythematosus (see page 794). If the eyelids are involved, then they may become edematous and shut, thereby resembling angioedema (see page 356). The affected area is painful, bright red, well circumscribed, swollen, indurated, and warm to the touch (Fig. 5-3). Often the affected skin will demonstrate a surface texture that resembles an orange peel (peau d’orange). High fever and lymphadenopathy often are present. Lymphangitis, leukocytosis, nausea, and vomiting occur infrequently. Diagnostic confirmation is difficult because cultures usually are not beneficial.

TREATMENT AND PROGNOSIS: The treatment of choice is penicillin. Alternative antibiotic drugs include macrolides such as erythromycin, cephalosporins such as cephalexin, and fluoroquinolones such as ciprofloxacin. On initiation of therapy, the area of skin involvement often enlarges, probably secondary to the release of toxins from the dying streptococci. A rapid resolution is noted within 48 hours. Without appropriate therapy, possible complications include abscess formation, gangrene, necrotizing fasciitis, toxic shock syndrome with possible multiple organ failure, thrombophlebitis, acute glomerulonephritis, septicemia, endocarditis, and death. Recurrences may develop in the same area, most likely in a previous zone of damaged lymphatics or untreated athlete’s foot. With repeated recurrences, permanent and disfiguring enlargements may result. In cases with multiple recurrences, prophylaxis with oral penicillin has been used.

CLINICAL FEATURES: Although the infection can occur at any age, the greatest prevalence occurs in children 5 to 15 years old, with most cases in temperate climates arising in the winter or early spring. The signs and symptoms of tonsillitis and pharyngitis vary from mild to intense. Common findings include sudden onset of sore throat, temperature of 101° to 104° F, dysphagia, tonsillar hyperplasia, redness of the oropharynx and tonsils, palatal petechiae, cervical lymphadenopathy, and a yellowish tonsillar exudate that may be patchy or confluent (Fig. 5-4). Other occasional findings include a “beefy” red and swollen uvula, excoriated nares, and a scarlatiniform rash (see next topic). Systemic symptoms, such as headache, malaise, anorexia, abdominal pain, and vomiting, may be noted, especially in younger children. Conjunctivitis, coryza (rhinorrhea), cough, hoarseness, discrete ulcerative lesions, anterior stomatitis, absence of fever, a viral exanthem, and diarrhea typically are associated with the viral infections and normally are not present in streptococcal pharyngotonsillitis.

DIAGNOSIS: Although the vast majority of pharyngitis cases are caused by a viral infection, reviews have shown that about 70% of adults in the United States receive antibiotic therapy. In an attempt to minimize overuse, antibiotics should not be prescribed without confirmation of bacterial infection. Except for very rare infections such as Corynebacterium diphtheriae (see page 186) and Neisseria gonorrhoeae (see page 193), antibiotics are of no benefit for acute pharyngitis except for those related to group A streptococci.

Patients exhibiting features strongly suggestive of a viral infection (see previous section) should not receive antibiotic therapy or microbiologic testing for streptococcal infection. Because the clinical features of streptococcal pharyngitis overlap those of viral origin, the diagnosis cannot be based solely on clinical features; however, laboratory testing of all patients with sore throat cannot be justified. Diagnostic testing is recommended only for those patients with clinical and epidemiologic findings that suggest streptococcal infection or for those in close contact with a well-documented case. Although less sensitive than throat culture, rapid antigen detection testing provides quick results and exhibits good sensitivity and specificity. If negative results are obtained in children, then confirmatory throat cultures should be performed.

TREATMENT AND PROGNOSIS: Streptococcal pharyngitis usually is self-limited and resolves spontaneously within 3 to 4 days after onset of symptoms. In addition to reducing the localized morbidity of the infection, the main goals of therapy are to prevent development of acute rheumatic fever and complications such as peritonsillar or retropharyngeal abscess, deep tissue cellulitis, toxic shock–like syndrome, bacteremia, arthralgia, and acute glomerulonephritis. Initiation of appropriate therapy within the first 9 days after development of the pharyngitis will prevent rheumatic fever. Patients are considered noncontagious 24 hours after initiation of appropriate antibiotic therapy.

Group A streptococci are uniformly sensitive to penicillin. Although oral penicillin remains the therapy of choice, amoxicillin and cephalosporin drugs such as cephalexin, cefadroxil, cefuroxime, and cefprozil also are effective. Erythromycin is used in patients who have a known sensitivity to penicillin. Newer macrolides (e.g., clarithromycin, azithromycin) have similar effectiveness but cause less gastrointestinal distress when compared with erythromycin.

No single regimen eliminates pharyngeal pathogenic streptococci in 100% of treated patients. Posttherapeutic laboratory testing is recommended in patients with a family history of rheumatic fever, during outbreaks of acute rheumatic fever or streptococcal glomerulonephritis, during outbreaks of streptococcal pharyngitis in semiclosed communities, and when “ping pong” spread is occurring within a family. In these cases, clindamycin or amoxicillin-clavulanic acid often is able to clear the organism in patients who continue to demonstrate positive culture after penicillin therapy.

CLINICAL FEATURES: Scarlet fever is most common in children from the ages of 3 to 12 years. The enanthem of the oral mucosa involves the tonsils, pharynx, soft palate, and tongue (see discussion of streptococcal pharyngotonsillitis in previous section). The tonsils, soft palate, and pharynx become erythematous and edematous, and the tonsillar crypts may be filled with a yellowish exudate. In severe cases, the exudates may become confluent and can resemble diphtheria (see page 186).

Scattered petechiae may be seen on the soft palate. During the first 2 days, the dorsal surface of the tongue demonstrates a white coating through which only the fungiform papillae can be seen; this has been called white strawberry tongue (Fig. 5-5). By the fourth or fifth day, red strawberry tongue develops when the white coating desquamates to reveal an erythematous dorsal surface with hyperplastic fungiform papillae.

Classically, in untreated cases, fever develops abruptly around the second day. The patient’s temperature peaks at approximately 103° F and returns to normal within 6 days. The exanthematous rash develops within the first 2 days and becomes widespread within 24 hours. The classic rash of scarlet fever is distinctive and often is described as “a sunburn with goose pimples.” Pinhead punctate areas that are normal in color project through the erythema, giving the skin of the trunk and extremities a sandpaper texture. The rash is more intense in areas of pressure and skin folds. Often, transverse red streaks, known as Pastia’s lines, occur in the skin folds secondary to the capillary fragility in these zones of stress. In contrast, the skin of the face usually is spared or may demonstrate erythematous cheeks with circumoral pallor.

The rash usually clears within 1 week, and then a period of desquamation of the skin occurs. This scaling begins on the face at the end of the first week and spreads to the rest of the skin by the third week, with the extremities being the last affected. The desquamation of the face produces small flakes; the skin of the trunk comes off in thicker, larger flakes. This period of desquamation may last from 3 to 8 weeks.

DIAGNOSIS: A culture of throat secretions may be used to confirm the diagnosis of streptococcal infection, but this has been replaced by several methods of rapid detection of antigens that are specific for group A, b-hemolytic streptococci. Failure to respond to appropriate antibiotics should alert the clinician that the detected streptococci may represent an intercurrent carrier state, and other causes of infection should be investigated.

TREATMENT AND PROGNOSIS: Treatment of scarlet fever and the associated streptococcal pharyngitis is necessary to prevent the possibility of complications, such as peritonsillar or retropharyngeal abscess, sinusitis, or pneumonia. Late complications are rare and include otitis media, acute rheumatic fever, glomerulonephritis, arthralgia, meningitis, and hepatitis. The treatment of choice is oral penicillin, with erythromycin reserved for patients who are allergic to penicillin. Ibuprofen can be used to reduce the fever and relieve the associated discomfort. The fever and symptoms show dramatic improvement within 48 hours after the initiation of treatment. With appropriate therapy, the prognosis is excellent.

CLINICAL AND RADIOGRAPHIC FEATURES: Although tonsillar concretions and tonsilloliths are not uncommon, published reports are rare, often documenting unusually large examples. The affected tonsil will demonstrate one or more enlarged crypts filled with yellow debris that varies in consistency from soft to friable to fully calcified. In contrast to acute tonsillitis, the surrounding tonsillar tissue is not acutely painful, dramatically inflamed, or significantly edematous. Tonsilloliths can develop over a wide age range, from childhood to old age, with a mean patient age in the early 40s. Men are affected twice as frequently as women. These calcifications vary from small clinically insignificant lesions to massive calcifications more than 14 cm in length. Tonsilloliths may be single or multiple, and bilateral cases have been reported.

Many tonsillar concretions and tonsilloliths, especially the smaller examples, are asymptomatic. However, these calcifications can promote recurrent tonsillar infections and may lead to pain, abscess formation, ulceration, dysphagia, chronic sore throat, irritable cough, otalgia, or halitosis. Occasionally, patients will report a dull ache or a sensation of a foreign object in the throat that is relieved on removal of the tonsillar plug. In patients with large stones, clinical examination often reveals a hard, yellow submucosal mass of the affected tonsil. In older adult patients, large tonsilloliths can be aspirated and produce significant secondary pulmonary complications. Most frequently, tonsilloliths are discovered on panoramic radiographs as radiopaque objects superimposed on the midportion of the mandibular ramus (Fig. 5-6). On occasion, calcifications initially thought to be bilateral are proven to be unilateral with a panoramic ghost image present on the contralateral side.

DIAGNOSIS: A strong presumptive diagnosis can be made through a combination of the clinical and radiographic features. After detection on a panoramic radiograph, if further diagnostic confirmation of tonsilloliths is deemed necessary, then their presence can be confirmed with computed tomography (CT), magnetic resonance imaging (MRI), or the demonstration of the calculi on removal of the affected tonsil.

TREATMENT AND PROGNOSIS: Tonsilloliths discovered incidentally during evaluation of a panoramic radiograph often are not treated unless associated with significant tonsillar hyperplasia or clinical symptoms. Affected individuals occasionally try to remove tonsillar concretions with instruments such as straws, toothpicks, and dental instruments. Such therapy has the potential to damage the surrounding tonsillar tissue and should be discouraged. Patients should be educated to attempt removal by gargling warm salt water or using pulsating jets of water.

Superficial calculi can be enucleated or curetted; deeper tonsilloliths require local excision. Redevelopment of removed concretions is common. One group successfully used laser cryptolysis to reduce the extent of the tonsillar invaginations and stop the redevelopment of the concretions. If evidence of associated chronic tonsillitis is seen, then tonsillectomy provides definitive therapy.

CLINICAL FEATURES: The signs and symptoms of diphtheria arise 1 to 5 days after exposure to the organism. The initial systemic symptoms, which include low-grade fever, headache, malaise, anorexia, sore throat, and vomiting, arise gradually and may be mild. Although skin wounds may be involved, the infection predominantly affects mucosal surfaces and may produce exudates of the nasal, tonsillar, pharyngeal, laryngotracheal, conjunctival, or genital areas. Involvement of the nasal cavity is often accompanied with prolonged mucoid or hemorrhagic discharge. The oropharyngeal exudate begins on one or both tonsils as a patchy, yellow-white, thin film that thickens to form an adherent gray covering. With time, the membrane may develop patches of green or black necrosis. The superficial epithelium is an integral portion of this exudate, and attempts at removal are difficult and may result in bleeding. The covering may continue to involve the entire soft palate, uvula, larynx, or trachea, resulting in stridor and respiratory difficulties. Palatal perforation has rarely been reported.

During the Russian epidemic, patients with lesions isolated to the oral cavity were documented. In these patients, scattered areas of necrosis were noted on the buccal mucosa, upper and lower lips, hard and soft palate, or tongue. Such localization is rare and makes diagnosis more difficult.

The severity of the infection correlates with the spread of the membrane. Local obstruction of the airway can be lethal. Involvement of the tonsils leads to significant cervical lymphadenopathy, which often is associated with an edematous neck enlargement known as bull neck. Toxin-related paralysis may affect oculomotor, facial, pharyngeal, diaphragmatic, and intercostal muscles. The soft palatal paralysis can lead to nasal regurgitation during swallowing. Oral or nasal involvement has been reported to spread to the adjacent skin of the face and lips.

Cutaneous diphtheria can occur anywhere on the body and is characterized by chronic skin ulcers that frequently are associated with infected insect bites and also may harbor other pathogens such as Staphylococcus aureus or Streptococcus pyogenes. These skin lesions can arise even in vaccinated patients and typically are not associated with systemic toxic manifestations. When contracted by travelers from developed nations, the diagnosis often is delayed because of the nonspecific clinical presentation and a low index of suspicion. The cutaneous lesions represent an important reservoir of infection and can lead to more typical and lethal diphtheria in unprotected contacts.

Although bacteremia is rare, circulating toxin can result in systemic complications. Myocarditis and neurologic difficulties are seen most frequently and are usually discovered in patients with severe nasopharyngeal diphtheria. Myocarditis may exhibit as progressive weakness and dyspnea or lead to acute congestive heart failure. Neuropathy is not uncommon in patients with severe diphtheria, and palatal paralysis is the most commonly seen manifestation. A peripheral polyneuritis resembling Guillain-Barré syndrome also may occur.

DIAGNOSIS: Although the clinical presentation can be distinctive in severe cases, laboratory confirmation should be sought in all instances. The specimen for culture should be obtained from underneath the diphtheric membrane, if possible, or from the surface of the membrane. Culture material also should be obtained from the nasal mucosa. Diphtheria also must be kept in mind for any patient who has traveled to a disease-endemic area and has chronic skin ulcerations. In these cases, wound swab specimens should be examined for C. diphtheriae.

TREATMENT AND PROGNOSIS: Treatment of the patient with diphtheria should be initiated at the time of the clinical diagnosis and should not be delayed until the results of the culture are received. Antitoxin should be administered in combination with antibiotics to prevent further toxin production, to stop the local infection, and to prevent transmission. Erythromycin, procaine penicillin, or intravenous (IV) penicillin may be used. Most patients are no longer infectious after 4 days of antibiotic therapy, but some may retain vital organisms. The patient is not considered to be cured until three consecutive negative culture specimens are obtained.

Before the development of the antitoxin, the mortality rate approached 50%, usually from cardiac or neurologic complications. The current mortality rate is less than 5%, but the outcome is unpredictable. Development of myocarditis is an important predictor of mortality.

Deaths still occur in the United States because of delays in therapy secondary to lack of suspicion. With worldwide travel and visitors from across the globe, prevention is paramount. Even in those vaccinated as children, it must be remembered that a booster inoculation is required every 10 years.

CLINICAL FEATURES:

HISTOPATHOLOGIC FEATURES: The histopathologic picture of the oral lesions in the syphilitic patient is not specific. During the first two stages, the pattern is similar. The surface epithelium is ulcerated in primary lesions and may be ulcerated or hyperplastic in the secondary stage. The underlying lamina propria may demonstrate an increase in the number of vascular channels, and an intense chronic inflammatory reaction is present. The infiltrate is composed predominantly of lymphocytes and plasma cells and often demonstrates a perivascular pattern (Fig. 5-16). Although the presence of plasma cells within the infiltrate may suggest the diagnosis of syphilis on the skin, their presence in areas of oral ulceration is commonplace and therefore not necessarily of diagnostic significance. In secondary syphilis, ulceration may not be present and the surface epithelium often demonstrates hyperplasia with significant spongiosis and exocytosis (Fig. 5-17). When noted in combination with an underlying dense, deep, and perivascular plasmacytic infiltrate, the index of suspicion often raises to a level that supports a search for the organism. The use of special silver impregnation techniques, such as Warthin-Starry or Steiner stains, or immunoperoxidase reactions directed against the organism often show scattered corkscrewlike spirochetal organisms that frequently are found most easily within the surface epithelium (see Fig. 5-17, C). The organism also can be detected in tissue through direct fluorescent antibody testing.

Oral tertiary lesions typically exhibit surface ulceration, with peripheral pseudoepitheliomatous hyperplasia. The underlying inflammatory infiltrate usually demonstrates foci of granulomatous inflammation with well-circumscribed collections of histiocytes and multinucleated giant cells. Even with special stains, the organisms are hard to demonstrate in the third stage; researchers believe the inflammatory response is an immune reaction, rather than a direct response to T. pallidum.

DIAGNOSIS: The diagnosis of syphilis can be confirmed by demonstrating the spiral organism by dark-field examination of a smear of the exudate of an active lesion. False-positive results are possible in the oral cavity because of morphologically similar oral inhabitants, such as Treponema microdentium, T. macrodentium, and T. mucosum. Demonstration of the organism on a smear or in biopsy material should be confirmed through the use of specific immunofluorescent antibody or serologic tests.

Several nonspecific and not highly sensitive serologic screening tests for syphilis are available. These include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR). After the first 3 weeks of infection, the screening tests are positive strongly throughout the first two stages. After the development of latency, the positivity generally subsides with time. As part of appropriate prenatal care, all pregnant women should receive one of the nonspecific screening tests.

Specific and highly sensitive serologic tests for syphilis also are available. These include the fluorescent treponemal antibody absorption (FTA-ABS), T. pallidum hemagglutination assay (TPHA), T. pallidum particle agglutination assay (TPPA), and microhemagglutination assay for antibody to T. pallidum (MHA-TP). These test results become positive at the time of the development of the first lesion of primary syphilis and remain positive for life. This lifelong persistence of positivity limits their usefulness in the diagnosis of a second incidence of infection. Therefore, in cases of possible reinfection, the organisms should be demonstrated within the tissue or exudates.

TREATMENT AND PROGNOSIS: The treatment for syphilis necessitates an individual evaluation and a customized therapeutic approach. The treatment of choice is penicillin. The dose and administration schedules vary according to the stage, neurologic involvement, and immune status. For primary, secondary, or early latent syphilis, a single dose of parenteral long-acting benzathine penicillin G is given. For late latent or tertiary syphilis, intramuscular penicillin is administered weekly for 3 weeks. For the patient with a true penicillin allergy, doxycycline is second-line therapy, although tetracycline, erythromycin, and ceftriaxone also have demonstrated antitreponemal activity.

In 50% of patients with primary syphilis and 90% of those with secondary syphilis, an unusual initial response to therapy occurs known as the Jarisch-Herxheimer reaction. This process occurs secondary to release of endotoxin when antibiotics kill large numbers of organisms. Clinical evidence of this reaction occurs about 8 hours after the first injection of penicillin and most commonly includes mild fever, malaise, headache, and an exacerbation of skin or mucosal lesions. These signs and symptoms are very temporary and rapidly fade.

Treatment failures occur in approximately 5% of patients. When treating primary, secondary, or early latent syphilis, some experts recommend serologic follow-up at 6, 12, 18, and 24 months. Pregnant women treated for syphilis should be retested at the twenty-eighth week and again at delivery. Infants born to seropositive mothers are treated with IV penicillin.

Even in patients who obtain a clinical and serologic “cure” with penicillin, it must be remembered that T. pallidum can escape the lethal effects of the antibiotic when the organism is located within the confines of lymph nodes or the central nervous system. Therefore, antibiotic therapy may not always result in a total cure in patients with neurologic involvement but may arrest only the clinical presentations of the infection. Patients with immunosuppression, such as those with AIDS, may not respond appropriately to standard antibiotic regimens, and numerous reports have documented a continuation to neurosyphilis despite seemingly appropriate single-dose therapy.

In the review of the recent increase of syphilis in MSM, high rates of coinfection with HIV have been documented. Although many factors are involved, the mucosal damage created by the spirochetes probably provides greater access for HIV infection. Patients diagnosed with syphilis, especially MSM, also should be tested for HIV.

CLINICAL FEATURES: The infection is spread through sexual contact, and most lesions occur in the genital areas. Indirect infection is rare because the organism is sensitive to drying and cannot penetrate intact stratified squamous epithelium. The incubation period is typically 2 to 5 days. Affected areas often demonstrate significant purulent discharge, but approximately 10% of men and up to 80% of women who contract gonorrhea are asymptomatic.

In men the most frequent site of infection is the urethra, resulting in purulent discharge and dysuria. Less common primary sites include the anorectal and pharyngeal areas. The cervix is the primary site of involvement in women, and the chief complaints are increased vaginal discharge, intermenstrual bleeding, genital itching, and dysuria. The organism may ascend to involve the uterus and ovarian tubes, leading to the most important female complication of gonorrhea—pelvic inflammatory disease (PID). The symptoms of PID include cramps and abnormal bleeding, which may be severe or mild. The long-term complications of PID include ectopic pregnancies or infertility from tubal obstruction.

Between 0.5% and 3.0% of untreated patients with gonorrhea will have disseminated gonococcal infections from systemic bacteremia. The most common signs of dissemination are myalgia, arthralgia, polyarthritis, and dermatitis. In 75% of patients with disseminated disease, a characteristic skin rash develops. The dermatologic lesions consist of discrete papules and pustules that often exhibit a hemorrhagic component and occur primarily on the extremities. Less common alterations secondary to gonococcal septicemia include fever, endocarditis, pericarditis, meningitis, and oral mucosal lesions of the soft palate and oropharynx, which are similar to aphthous ulcerations.

The prevalence of oral sex appears to be increasing and is thought by many to be the result of the misconception that it represents a low-risk sexual practice and a safe alternative to high-risk activities such as anal or vaginal sex. Most cases of oral gonorrhea appear to be a result of fellatio, although oropharyngeal gonorrhea may be the result of gonococcal septicemia, kissing, or cunnilingus. Therefore, the majority of oropharyngeal gonorrhea cases have been reported in women or homosexual men. Another contributing problem is that pharyngeal gonorrhea often is asymptomatic, making delay in diagnosis and spread more likely. In a recent review of 200 men with urethral gonorrhea, more than 50% admitted to having sex with men (i.e., MSM), and 58% of the MSM group identified oral sex as the sole risk factor for their infection.

The most common site of oropharyngeal involvement is the pharynx along with the tonsils and uvula. Although pharyngeal gonorrhea usually is asymptomatic, a mild-to-moderate sore throat may occur and be accompanied by nonspecific, diffuse oropharyngeal erythema. Involved tonsils typically demonstrate edema and erythema, often with scattered, small punctate pustules. Although most cases of pharyngeal infection resolve spontaneously without adverse sequelae, treatment is important to reduce the potential for spreading the infection.

Rarely, lesions have been reported in the anterior portion of the oral cavity, with areas of infection appearing erythematous, pustular, erosive, or ulcerated. Occasionally, the infection may simulate necrotizing ulcerative gingivitis (NUG), but some clinicians have reported that the typical fetor oris is absent, providing an important clue to the actual cause (Fig. 5-18). Submandibular or cervical lymphadenopathy may be present.

During birth, infection of an infant’s eyes can occur from an infected mother who may be asymptomatic. This infection is called gonococcal ophthalmia neonatorum and can rapidly cause perforation of the globe of the eye and blindness. Common signs of infection include significant conjunctivitis and a mucopurulent discharge from the eye.

DIAGNOSIS: In males with a urethral discharge, a Gram stain of the purulent material can be used to demonstrate gram-negative diplococci within the neutrophils; additional testing usually is not indicated. Although Gram stains may be beneficial in women, confirmation of the diagnosis is recommended by culture of endocervical swabs if conditions are adequate to maintain viability of the organisms. A number of other diagnostic studies have been available for many years. Nucleic acid amplification tests (NAATs) amplify and detect N. gonorrhoeae–specific DNA or RNA sequences and are recommended for the diagnosis when conditions are not adequate to maintain the viability of the organisms. In spite of the availability of NAATs, culture remains the preferred diagnostic method for diagnosis of oropharyngeal infections.

TREATMENT AND PROGNOSIS: The primary therapy for gonorrhea has been fluoroquinolones such as ciprofloxacin, levofloxacin, or ofloxacin; however, increasing resistance has been documented in MSM and in infections acquired in Asia, the Pacific islands (including Hawaii), and California. Although oral ciprofloxacin remains first-line therapy for most patients, those at risk for resistant disease should receive intramuscular ceftriaxone. Oral cefixime also is effective but currently is not available in the United States in an appropriate formulation. Patients with gonorrhea are at risk for additional sexually transmitted diseases, most commonly Chlamydia trachomatis for which a C. trachomatis–specific NAAT is available. If chlamydia has not been ruled out, then affected patients also should receive either azithromycin or doxycycline. Rescreening is recommended 1 to 2 months after therapy. The most common cause for treatment failure is reexposure to infected partners, who often are asymptomatic; therefore, the treatment of all recent sexual partners is recommended. Truly resistant infections should be cultured with antimicrobial testing and selection of an appropriate alternate antibiotic. Prophylactic ophthalmic erythromycin, tetracycline, or silver nitrate is applied to the newborn’s eyes to prevent the occurrence of gonococcal ophthalmia neonatorum.

CLINICAL AND RADIOGRAPHIC FEATURES: Primary TB is usually asymptomatic. Occasionally, fever and pleural effusion may occur.

Classically, the lesions of secondary TB are located in the apex of the lungs but may spread to many different sites by expectorated infected material or through the lymphatic or vascular channels. Typically, patients have a low-grade fever, malaise, anorexia, weight loss, and night sweats. With pulmonary progression, a productive cough develops, often with hemoptysis or chest pain. Progressive TB may lead to a wasting syndrome that, in the past, was termed consumption, because it appeared that the patient’s body was being consumed or destroyed.

Extrapulmonary TB is seen and represents an increasing proportion of the currently diagnosed cases. In patients with AIDS, more than 50% will have extrapulmonary lesions. Any organ system may be involved, including the lymphatic system, skin, skeletal system, CNS, kidneys, and gastrointestinal tract. Involvement of the skin may develop and has been called lupus vulgaris.

Head and neck involvement may occur. The most common extrapulmonary sites in the head and neck are the cervical lymph nodes followed by the larynx and middle ear. Much less common sites include the nasal cavity, nasopharynx, oral cavity, parotid gland, esophagus, and spine.

Oral lesions of TB are uncommon, with most cases appearing as a chronic painless ulcer. Less frequent presentations include nodular, granular, or (rarely) firm leukoplakic areas. The majority of the lesions represent secondary infection from the initial pulmonary foci, occurring most frequently in middle-aged adults. It is unclear whether these lesions develop from hematogenous spread or from exposure to infected sputum. The reported prevalence of clinically evident oral lesions varies from 0.5% to 5.0%. However, one autopsy study revealed a prevalence of close to 20% when the tongues of those infected were examined microscopically. The discovery of pulmonary TB as a result of the investigation of oral lesions occurs but is unusual. Primary oral TB without pulmonary involvement is rare and is more common in children and adolescents.

When present, primary oral TB usually involves the gingiva, mucobuccal fold, and areas of inflammation adjacent to teeth or in extraction sites; secondary oral lesions are mostly present on the tongue, palate, and lip (Figs. 5-19 and 5-20). Primary oral lesions are usually associated with enlarged regional lymph nodes. Tuberculous osteomyelitis has been reported in the jaws and appears as ill-defined areas of radiolucency.

Nontuberculous mycobacterial infections from contaminated milk are currently rare in the industrialized world because of pasteurization of milk, as well as rapid identification and elimination of infected cows. Drinking contaminated milk can result in a form of mycobacterial infection known as scrofula. Scrofula is characterized by enlargement of the oropharyngeal lymphoid tissues and cervical lymph nodes (Fig. 5-21). On occasion, the involved nodes may develop significant caseous necrosis and form numerous sinus tracts through the overlying skin (Fig. 5-22). In addition, areas of nodal involvement may radiographically appear as calcified lymph nodes that may be confused with sialoliths (Fig. 5-23). Pulmonary involvement is unusual in patients with scrofula.

HISTOPATHOLOGIC FEATURES: The cell-mediated hypersensitivity reaction is responsible for the classic histopathologic presentation of TB. Areas of infection demonstrate the formation of granulomas, which are circumscribed collections of epithelioid histiocytes, lymphocytes, and multinucleated giant cells, often with central caseous necrosis (Fig. 5-24). In a person with TB, one of these granulomas is called a tubercle. Special stains, such as the Ziehl-Neelsen or other acid-fast stains, are required to demonstrate the mycobacteria (Fig. 5-25). Because of the relative scarcity of the organisms within tissue, the special stains successfully demonstrate the organism in only 27% to 60% of cases. Therefore, a negative result does not completely rule out the possibility of TB.

DIAGNOSIS: Approximately 2 to 4 weeks after initial exposure, a cell-mediated hypersensitivity reaction to tubercular antigens develops. This reaction is the basis for the purified protein derivative (PPD) skin test (i.e., tuberculin skin test), which uses a filtered precipitate of heat-sterilized broth cultures of M. tuberculosis. Positivity runs as high as 80% in developing nations; only 5% to 10% of the population in the United States is positive. A positive tuberculin skin test result indicates exposure to the organism and does not distinguish infection from active disease. A negative tuberculin skin test result does not totally rule out the possibility of TB. False-negative reactions have been documented in older adults; the immunocompromised; patients with sarcoidosis, measles, or Hodgkin’s lymphoma; and when the antigen was placed intradermally. The false-negative rate may be as high as 66% in patients with AIDS.

Special mycobacterial stains and culture of infected sputum or tissue must be used to confirm the diagnosis of active disease. Even if detected with special stains, identification of the organism by culture is appropriate. This identification is important because some forms of nontuberculous mycobacteria have a high level of resistance to traditional antituberculous therapy and frequently require surgical excision. Because 4 to 6 weeks may be required to identify the organism in culture, antituberculous therapy often is initiated before definitive classification. Polymerase chain reaction (PCR) is also used to identify M. tuberculosis DNA and speeds the diagnosis without the need to await culture results.

TREATMENT AND PROGNOSIS: M. tuberculosis can mutate and develop resistance to single-agent medications. To combat this ability, multiagent therapy is the treatment of choice for an active infection, and treatment usually involves two or more active drugs for several months to years. A frequently used protocol consists of an 8-week course of isoniazid, rifampin, and pyrazinamide, followed by a 16-week course of isoniazid and rifampin. Other first-line medications include ethambutol and streptomycin. Relapse rates of approximately 1.5% are seen. With an alteration of doses and the administration schedule, the response to therapy in patients with AIDS has been good, but relapses and progression of infection have been seen.

A different protocol termed chemoprophylaxis is used for patients who have a positive PPD skin test but no signs or symptoms of active disease. Although this situation does not mandate therapy, several investigators have demonstrated the value of therapy, especially in young individuals. Bacillus Calmette-Guérin (BCG) vaccine for TB is available to approximately 85% of the global population, but its use is restricted in the United States because of a controversy related to its effectiveness.

CLINICAL FEATURES: Currently, leprosy is classified into two separate categories, paucibacillary and multibacillary, with the distinction influencing the recommended form of therapy. Because laboratory services such as skin smears often are not available, patients are increasingly being classified on clinical grounds using the number of lesions (primarily skin) and the number of body areas affected.

Paucibacillary leprosy corresponds closely to the tuberculoid pattern of leprosy and exhibits a small number of well-circumscribed, hypopigmented skin lesions. Nerve involvement usually results in anesthesia of the affected skin, often accompanied by a loss of sweating. Oral lesions are rare in this variant.

Multibacillary leprosy corresponds well to the lepromatous pattern of leprosy and begins slowly with numerous, ill-defined, hypopigmented macules or papules on the skin that, with time, become thickened (Fig. 5-26). The face is a common site of involvement, and the skin enlargements can lead to a distorted facial appearance (leonine facies). Hair, including the eyebrows and lashes, often is lost (Fig. 5-27). Nerve involvement leads to a loss of sweating and decreased light touch, pain, and temperature sensors. This sensory loss begins in the extremities and spreads to most of the body. Nasal involvement results in nosebleeds, stuffiness, and a loss of the sense of smell. The hard tissue of the floor, septum, and bridge of the nose may be affected. Collapse of the bridge of the nose is considered pathognomonic.

Oral lesions are not rare in multibacillary leprosy, and reports on their prevalence vary from 19% to 60%. In an excellent review by Prabhu and Daftary of 700 patients with leprosy, the prevalence of facial skin involvement was 28%, and oral lesions were noted in 11.5%. The lesions tended to be more frequent during the first 5 years of the disease.

The sites that are cooled by the passage of air appear to be affected most frequently. The locations affected in order of frequency are the hard palate, soft palate, labial maxillary gingiva, tongue, lips, buccal maxillary gingiva, labial mandibular gingiva, and buccal mucosa. Affected soft tissue initially appears as yellowish to red, sessile, firm, enlarging papules that develop ulceration and necrosis, followed by attempted healing by secondary intention. Continuous infection of an area can lead to significant scarring and loss of tissue. Complete loss of the uvula and fixation of the soft palate may occur. The lingual lesions appear primarily in the anterior third and often begin as areas of erosion, which may develop into large nodules. Infection of the lip can result in significant macrocheilia, which can be confused clinically and microscopically with cheilitis granulomatosa (see page 342).

Direct infiltration of the inflammatory process associated with lepromatous leprosy can destroy the bone underlying the areas of soft tissue involvement. Often the infection creates a unique pattern of facial destruction that has been termed facies leprosa and demonstrates a triad of lesions consisting of atrophy of the anterior nasal spine, atrophy of the anterior maxillary alveolar ridge, and endonasal inflammatory changes. Involvement of the anterior maxilla can result in significant bone erosion, with loss of the teeth in this area. Maxillary involvement in children can affect the developing teeth and produce enamel hypoplasia and short tapering roots. Dental pulp infection can lead to internal resorption or pulpal necrosis. Teeth with pulpal involvement may demonstrate a clinically obvious red discoloration of the crown. The cause of the discoloration is unknown but appears to be related to intrapulpal vascular damage secondary to the infection. Granulomatous involvement of the nasal cavity can erode through the palatal tissues and result in perforation.

The facial and trigeminal nerves can be involved with the infectious process. Facial paralysis may be unilateral or bilateral. Sensory deficits may affect any branch of the trigeminal nerve, but the maxillary division is the most commonly affected.

HISTOPATHOLOGIC FEATURES: Biopsy specimens of paucibacillary leprosy typically reveal the tuberculoid pattern that demonstrates granulomatous inflammation with well-formed clusters of epithelioid histiocytes, lymphocytes, and multinucleated giant cells (Fig. 5-28). A paucity of organisms exists; when present, they can be demonstrated only when stained with acid-fast stains, such as the Fite method. Multibacillary leprosy is associated with a lepromatous pattern that demonstrates no well-formed granulomas; the typical finding is sheets of lymphocytes intermixed with vacuolated histiocytes known as lepra cells (Fig. 5-29). Unlike tuberculoid leprosy, an abundance of organisms can be demonstrated with acid-fast stains in the lepromatous variant (Fig. 5-30). It has been reported that the organism can be found with special stains in 100% of lepromatous leprosy cases, 75% of borderline cases, and only 5% of tuberculoid cases.

DIAGNOSIS: The definitive diagnosis is based on the clinical presentation and supported by the demonstration of acid-fast organisms on a smear or in the tissue. The organism cannot be cultivated on artificial media, but M. leprae can be identified by using molecular biologic techniques. No reliable test is available to determine whether a person has been exposed to M. leprae without developing the disease; this creates difficulties in establishing the diagnosis and determining the prevalence of the infection.

TREATMENT AND PROGNOSIS: One of the major reasons for the decreasing prevalence of leprosy is the provision of an uninterrupted supply of free, high-quality medications in calendar blister packs to all patients regardless of the living conditions or remoteness of the location. Paucibacillary leprosy is treated with a 6-month regimen of rifampin and dapsone, whereas patients with multibacillary leprosy receive 24 months of rifampin, dapsone, and clofazimine. Long-term follow up is recommended because of occasional relapses. Patients allergic to rifampin are treated with a 24-month course of clofazimine, ofloxacin, and minocycline.

After resolution of the infection, the therapy must be directed toward reconstruction of the damage, in addition to physiotherapy and education of the patients who must live not only with their physical damage but also with the psychologic stigmata. As medical therapy becomes more successful, the number of long-term survivors of the infection increases. Worldwide, it is estimated that currently about 3 million individuals have leprosy-related impairments and disability.

CLINICAL FEATURES: Noma usually arises in children from 1 to 10 years of age, although it also can occur in adults with a major debilitating disease (e.g., diabetes mellitus, leukemia, lymphoma, HIV infection). The infection often begins on the gingiva as NUG, which may extend either facially or lingually to involve the adjacent soft tissue and form areas called necrotizing ulcerative mucositis. Zones of necrosis also may develop in soft tissue not continuous with the gingiva, particularly in areas of trauma (Fig. 5-31). The necrosis can extend into deeper tissues; over the next few days, zones of blue-black discoloration of the overlying skin surface may develop (Fig. 5-32). Often the necrotic zone is cone shaped, with a small point of cutaneous necrosis overlying a larger zone of oral mucosal destruction. Unlike other infections, the process does not follow tissue planes and tends to spread through anatomic barriers such as muscle. These discolored zones break down into areas of yellowish necrosis that also frequently spreads into adjacent bone, with large areas of osteomyelitis possible. In most instances the necrotic area is well defined and unilateral. Fetid odor, significant pain, fever, malaise, tachycardia, increased respiratory rate, anemia, leukocytosis, and regional lymphadenopathy are typical. Additional lesions also may occur in distant sites, such as the scalp, neck, ear, shoulders, chest, perineum, and vulva.

The majority of affected children also demonstrate significant stunting of growth. Although many families will have numerous children living in the same environment, those affected with noma typically are isolated, which suggests additional factors at work. Some have suggested that victims of intrauterine growth retardation and premature birth may be predisposed to future development of noma. Others have suggested that infection with certain herpesviruses, such as cytomegalovirus, may lower local immunity and promote development of noma.

TREATMENT AND PROGNOSIS: In addition to using appropriate antibiotics to treat noma, the clinician must direct therapeutic attention not only to local wound care but also toward correcting the inadequate nutrition, hydration, and electrolyte imbalances. Penicillin and metronidazole are the first-line therapeutic antibiotics for necrotizing stomatitis. The therapy of noma neonatorum is directed against the Pseudomonas organisms and often consists of piperacillin, gentamicin, or clindamycin. Conservative débridement of gross necrotic areas is recommended, but aggressive removal is contraindicated because it does not stop the extension of the process and compounds the reconstruction problems. Necrotic bone is left in place to help hold the facial form but is removed as it sequestrates. Reconstruction should be delayed for 1 year to ensure complete recovery.

Before the development of antibiotics, the mortality rate approached 95% and still remains high in many portions of the world. In the United States, fewer than 10% of appropriately treated patients die. Common causes of death include infectious complications, such as pneumonia, diarrhea, and septicemia. Noma infection can cause significant morbidity when it is not fatal. Facial disfigurement that affects the patient’s future growth and development is not rare. Reconstruction often is extremely challenging and should be delayed until healing is complete. Trismus from significant scarring associated with mandibular involvement can occur, but it can be countered with early postoperative and long-term physiotherapy. Noma neonatorum is much more dangerous because the septicemia that is related to Pseudomonas spp. infection is usually fatal.

CLINICAL FEATURES: Actinomycosis may be either an acute, rapidly progressing infection or a chronic, slowly spreading lesion that is associated with fibrosis. Approximately 55% of cases of actinomycosis are diagnosed in the cervicofacial region, with 25% occurring in the abdominal and pelvic region and 15% in the pulmonary system. The remaining 5% exhibits a variety of patterns, such as superficial skin infections, or infections of the genitourinary region (often linked to use of intrauterine contraceptive devices).

The suppurative reaction of the infection may discharge large yellowish flecks that represent colonies of the bacteria called sulfur granules. Although common, sulfur granules are not present invariably. In addition, another infection that also can produce sulfur granules and mimic actinomycosis is botryomycosis, an unrelated process that represents an unusual host reaction to Staphylococcus aureus and other bacteria.

In the cervicofacial region, the organism typically enters tissue through an area of prior trauma, such as a soft tissue injury, periodontal pocket, nonvital tooth, extraction socket, or infected tonsil. The infection does not spread along the typical fascial planes and usually disregards the normal lymphatic and vascular routes. Direct extension through soft tissue is seen, and lymph nodes become involved only if they are in the path of the process. The classic description is of a “wooden” indurated area of fibrosis, which ultimately forms a central, softer area of abscess. The infection may extend to the surface, forming a sinus tract (Fig. 5-33). Pain often is minimal. The soft tissues of the submandibular, submental, and cheek areas are common areas of involvement, with the area overlying the angle of the mandible being the most frequently affected site.

Localized abscesses without the associated chronic fibrosing reaction have been reported in soft tissue that has received minor trauma. The tongue is the most frequently mentioned site, but any oral mucosal location is possible. Involvement of the tonsillar crypts may produce infectious symptoms; in most cases, however, the primary change is one of variable hyperplasia. Tonsillar hyperplasia thought to be secondary to actinomycotic infestation of the crypts does not appear responsive to antibiotics, probably because of the superficial location of the bacterial colonies. Tonsillectomy is generally the most effective treatment for this situation.

Salivary gland involvement also is not unusual. Intraductal colonization by the organism may lead to infections in both the submandibular and parotid glands, resulting in abscess formation in the submandibular and masseter spaces, respectively. In addition, more localized infections occur in minor salivary gland ducts, which also may demonstrate mucous plugs or sialoliths.

Actinomycotic osteomyelitis of the mandible and maxilla has been reported. Trauma, periodontal infections, nonvital teeth, and extraction sites have all provided access. Ill-defined areas of radiolucency, often surrounded by radiopacity, may be found with or without involvement of the overlying soft tissue.

Intrabony colonization of dentigerous cysts without other significant clinical or radiographic spread has been reported. Periapical inflammatory lesions involved by the bacteria can result in lesions that are difficult to resolve with standard endodontic treatment, but such lesions typically remain localized and do not evolve into invasive cervicofacial actinomycosis.

HISTOPATHOLOGIC FEATURES: The tissue removed from areas of active infection demonstrates a peripheral band of fibrosis encasing a zone of chronically inflamed granulation tissue surrounding large collections of polymorphonuclear leukocytes and, with luck, colonies of organisms (Fig. 5-34). The colonies consist of club-shaped filaments that form a radiating rosette pattern (Fig. 5-35). With hematoxylin and eosin (H&E) stains, the central core stains basophilic and the peripheral portion is eosinophilic. Methenamine silver stains demonstrate the organisms well. If the colonies of actinomycetes become dis-placed from the exudate, then a rim of neutrophils typically clings to the periphery of the organisms.

DIAGNOSIS: The diagnosis of actinomycosis is achieved ideally by culture, but less than 50% of cases are positive because of the overgrowth of associated bacteria, prior antibiotic therapy, or improper anaerobic media conditions. Lacking positive culture results, a strong presumptive diagnosis can be obtained through a demonstration of the typical colonies in lesional biopsy material. The material for culture and histopathologic examination is typically obtained during surgical exploration, with fine-needle aspiration being a satisfactory substitute in many cases. Sulfur granules in infections other than actinomycosis are so rare that their demonstration strongly supports the diagnosis. If desired, then fluorescein-conjugated antiserum can be used on the granules to specifically identify the Actinomyces species.

TREATMENT AND PROGNOSIS: The treatment of choice for actinomycosis in chronic fibrosing cases is prolonged high doses of antibiotics in association with abscess drainage and excision of the sinus tracts. A high antibiotic concentration is required to penetrate larger areas of suppuration and fibrosis. Although penicillin remains the standard of care with no documented in vivo resistance, some clinicians believe amoxicillin represents a better first-choice antibiotic. Other investigators have demonstrated in vitro resistance to penicillin and recommend tetra-cycline, which is as effective as penicillin and is the drug of choice for patients with a known allergy to penicillin. Early cervicofacial actinomycosis typically responds to a 5- to 6-week course of penicillin; patients with deep-seated infections may require up to 12 months.

In cases of osteomyelitis caused by actinomycetes, antibiotic therapy alone often is associated with persistent disease. Adequate débridement appears to be the cornerstone of therapy and ultimately determines the success of the subsequent antibiotic treatment. When combined with appropriate surgery, a 3-month course of penicillin usually is curative. In resistant cases, repeated débridement should be combined with cultures to direct future antibiotic therapy. Care should be taken to ensure that colonization of bony sequestra by actinomycotic colonies is not mistaken for invasive actinomycotic osteomyelitis.

Several authors have indicated that localized acute actinomycotic infections may be treated more conservatively than the deep, chronic cases of actinomycosis. Localized periapical and pericoronal actinomycosis, tongue abscesses, and focal subacute sialadenitis with intraductal involvement frequently respond well to surgical removal of infected tissue. In these cases it appears best to reserve antibiotics for patients in whom local surgical excision fails.

CLINICAL FEATURES: Eighty percent of the cases occur in patients younger than 21 years of age. Cat-scratch disease begins as a papule or pustule that develops in 3 to 14 days along the initial scratch line (Fig. 5-36). The lymph node changes develop in approximately 3 weeks and often may be accompanied by fever or malaise (Fig. 5-37). Scratches on the face typically lead to submandibular lymphadenopathy, and the patient may be referred to dental practitioners to rule out an odontogenic infection. Often the primary site of trauma may have resolved by the time that the symptomatic lymphadenopathy is diagnosed. Therefore, cat-scratch disease must be considered strongly in the differential diagnosis of patients with unexplained symptomatic lymphadenopathy. In about half of the cases, a single node is involved. Multiple regional nodes are affected in about 20%, and nodal enlargement is discovered in multiple sites in about 33%. Suppuration is noted in approximately 10% of affected patients.

A few patients with cat-scratch disease demonstrate unusual presentations. The infection can appear as an intraoral mass in the buccal mucosa when lymphoid aggregates become involved from an adjacent cutaneous primary site. Scratches in the preauricular area may localize in parotid lymphoid tissue and can cause significant parotid pain or even temporary facial paralysis. Other less common problems include granulomatous osteomyelitis, arthralgias, encephalopathy, erythematous and maculopapular rashes, splenomegaly, hepatic lesions, thrombocytopenia, pneumonia, anemia, pleural effusions, and recurrent bacterial infections.

Primary lesions adjacent to the eye can result in a conjunctival granuloma that is associated with preauricular lymphadenopathy (oculoglandular syndrome of Parinaud); this pattern is thought to occur when an individual touches fur moistened with the cat’s saliva during grooming. When the individual rubs their eye, the organism is transmitted to the conjunctiva.

During the past 2 decades, an unusual subcutaneous vascular proliferation, histopathologically similar to histiocytoid hemangioma, has been recognized in patients with AIDS. This proliferation has been termed bacillary angiomatosis, with most cases being definitively associated with Bartonella henselae. In a minority of the cases, bacillary angiomatosis is caused by a related organism, B. quintana. The affected areas often resemble Kaposi’s sarcoma (see page 270) and appear as variable numbers of red-to-purple skin lesions. These may be macular, papular, or pedunculated and exhibit a widespread distribution on the skin. Pain and tenderness are common. The larger lesions are friable and bleed easily.

Oral lesions have been seen in bacillary angiomatosis and also may resemble Kaposi’s sarcoma. The affected areas may exhibit zones of alveolar bone loss or may be within the soft tissue and appear as a proliferative vascular lesion.

HISTOPATHOLOGIC FEATURES: The involved lymph nodes are enlarged as a result of significant cortical hyperplasia, which classically contains areas of stellate suppurative necrosis surrounded by a band of histiocytes and neutrophils (Fig. 5-38). In some cases, significant necrosis is absent, but areas of karyorrhexis are present around proliferations of plump vascular channels that often exhibit thickened eosinophilic walls. On staining with the Warthin-Starry method, cat-scratch bacilli are usually found in areas without significant necrosis. As the disease progresses and necrosis increases, the organisms become more difficult to identify. In addition, the Brown-Hopps method of gram staining may be used to highlight the bacilli. Recently, a commercially available monoclonal antibody against B. henselae has been used to demonstrate the organisms via immunoperoxidase techniques on paraffin-embedded material. Upon immunostaining, the organisms are highlighted dramatically, an important advance over the previous special stains. One downside is the failure of this specific antibody to react with the organisms in the exceptional cases of cat-scratch disease caused by B. quintana or B. clarridgeiae.

Bacillary angiomatosis reveals lobular proliferations of small blood vessels in an edematous to fibrotic stroma. The supporting connective tissue typically demonstrates a significant number of neutrophils and leukocytoclasis, important clues to the diagnosis. Also present are variably sized amphophilic and granular aggregates that upon Warthin-Starry staining prove to be masses of the causative bacteria.

DIAGNOSIS: Today the diagnosis of cat-scratch disease usually is established via serologic tests that demonstrate a high degree of sensitivity and specificity. The most widely used is an indirect fluorescent antibody assay for detecting antibodies to B. henselae. Another commercially available method is an enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to the organism. Polymerase chain reaction (PCR) techniques also are available but are not widely used.

TREATMENT AND PROGNOSIS: Cat-scratch disease is a self-limiting condition and normally resolves within 4 months. The use of local heat, analgesics, and aspiration of the node on suppuration is the typical pattern of therapy. If persistent discomfort makes nodal aspiration necessary, then drainage should be achieved with a needle that is tunneled into the node laterally through normal skin 1 to 2 cm away from the lesion. Incision directly into the node could result in a chronic draining sinus.

Although the organism has demonstrated sensitivity to a number of antibiotics in culture, the results in immunocompetent patients have been inconsistent and difficult to evaluate because the disease is self-limited in most cases. Antibiotics typically are reserved for those cases that demonstrate a prolonged course or severe involvement. Use of antibiotic drugs in patients with AIDS and bacillary angiomatosis has produced dramatic resolution within 2 days. Although a number of medications have been used successfully, the primary antibiotics used for cat-scratch disease or bacillary angiomatosis are azithromycin, erythromycin, doxycycline, rifampin, ciprofloxacin, and gentamicin.

CLINICAL AND RADIOGRAPHIC FEATURES: Presenting symptoms of acute sinusitis in adults include headache, fever, and facial pain over the affected sinus. Anorexia, photophobia, and malaise also may be seen. Anterior nasal or posterior pharyngeal discharge is present; it may be thick or thin in consistency and appear clear, mucoid, or purulent. Children, with their less complex sinuses, typically have only persistent cough, fever, and purulent rhinorrhea. Localized involvement of the maxillary sinus can occur as pain over the cheekbone, toothache, periorbital pain, or temporal headache. Maxillary sinusitis is associated with increased pain when the head is held upright and less discomfort when the patient is supine.

Chronic sinusitis is less diagnostic, and radiographic imaging becomes more important. Frequent complaints include facial pressure, pain, or a sensation of obstruction. In some cases, nonspecific symptoms, such as headache, sore throat, lightheadedness, or generalized fatigue, also may be present or even dominate. Radiographically, the involved sinus has a cloudy, increased density (Fig. 5-40).

At times, sinusitis can be confused with an odontogenic infection. In such cases, close examination of periapical radiographs, a thorough periodontal examination, and assessment of tooth vitality often will rule out or point to an odontogenic infection. A sinus infection should be strongly considered when patients complain of pain from several teeth, demonstrate tenderness over one or both of the maxillary sinuses, exhibit nasal congestion, or have a nasal discharge accompanied by a foul odor, fever, and headache.

In addition to the patient’s symptoms, the diagnosis in the past often was made by procedures such as transillumination and by plain radiographs, such as the Waters, Caldwell-Luc, lateral, and submental vertex views. Today, when the diagnosis is in question, many clinicians use nasal endoscopy and computed tomography (CT). Areas of infection and sites of improper drainage will be found. These techniques not only confirm the diagnosis but also pinpoint the primary pathologic alteration that led to the obstructive sinusitis.

An antrolith appears radiographically as a radio-dense focus within the sinus. The calcification often is seen in association with a thickening of the antral lining or diffuse clouding of the affected sinus.

TREATMENT AND PROGNOSIS: Although acute sinusitis is usually a self-limiting disease, antibiotics are frequently prescribed. Few placebo-controlled, double-blind, randomized clinical trials have been published, and the results are inconsistent. Although the supporting evidence is weak, the few well-performed trials suggest that patients with more severe signs and symptoms may benefit from an antibiotic, whereas those with less severe manifestations do not require antibiotic therapy.

If antibiotics are used, the first-line therapy for acute sinusitis in otherwise healthy patients is amoxicillin. Because of drug resistance, additional medications are used if the patient does not respond to the initial antibiotic. Amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, or cefaclor are good antibiotic drugs for resistant cases. Although topical decongestants shrink nasal membranes and improve ostial drainage, they are not recommended because of the resultant decreased ciliary function and decreased mucosal blood flow, which leads to impaired antibiotic delivery. The effect of systemic antihistamine and decongestant medications on sinusitis has not been studied adequately.

In otherwise healthy adult patients, chronic sinusitis that is not responsive to typical medical management often is corrected surgically. In the past, radical stripping of the diseased sinus mucosa was the therapy of choice. Today, nasal endoscopy has shown that sinusitis is a disease of obstruction and that mucosal inflammation is usually a secondary development. Functional endoscopic sinus surgery enlarges the ostial openings and corrects blockages in the ostiomeatal complex, often with a rapid resolution of the signs and symptoms (see Fig. 5-35). The surgery is delicate because it extends close to the orbit and the central nervous system. Each patient’s unique anatomy should be evaluated carefully by CT and nasal endoscopy before surgery.

Although endoscopic surgery is considered by many to be the current standard of care for chronic sinusitis, a few investigators still use the more invasive Caldwell-Luc procedure in selected patients. Although the Caldwell-Luc procedure is associated with a higher prevalence of significant complications, it also is associated with a lower number of reoperations when compared with the less invasive endoscopic procedure. Therefore, some clinicians continue to use the old technique in patients who demonstrate recurrent disease limited to the maxillary sinus and prefer a single major operation rather than multiple, less invasive procedures.

When the infection is isolated to a single maxillary sinus and associated with a odontogenic cause, the dental pathosis must be resolved in addition to treating the diseased sinus. Although the Caldwell-Luc procedure continues to be used, endoscopic shaver-assisted techniques are becoming more popular to perform an antrostomy and accomplish removal of pathoses, such as irreversibly diseased antral lining, polyps, tooth fragments, and foreign material. When the sinus disease is caused by an oroantral communication, defects less than 5 μm typically close spontaneously. With small openings, the defect can be covered and protected during the early stages of healing with a resorbable barrier such as an absorbable gelatin sponge. Oroantral fistulae larger that 5 μm should be closed primarily, but this should be done only after resolution of any associated acute infection within the associated sinus.

In children, continued medical management is the therapy of choice for uncomplicated acute or recurrent acute sinusitis. The anatomy in the child, with the decreased distance between the orbit and brain, increases the difficulty of any surgical procedure. Surgical management is indicated in only a small number of childhood sinusitis cases. Suppurative sinusitis extending into surrounding tissues or true chronic sinusitis caused by serious underlying systemic disease are examples of indications for the surgical management of sinus disease in a child.