ACUTE & CHRONIC SINUSITIS

Essentials of Diagnosis

• Fever, facial pain or pressure, headache, purulent nasal or postnasal discharge (PND), cough.

• Tenderness over the sinuses, PND, other signs of complications may be seen such as meningismus or periorbital cellulitis.

• Leukocytosis in some cases, sinus or blood cultures may be positive for S pneumoniae, H influenzae, or other bacteria.

• CT scan is a very sensitive method of detecting sinusitis.

General Considerations

Inflammation of the pseudostratified epithelium of the sinuses may occur as a result of an infection, allergy, toxin, or an autoimmune disorder. The paranasal sinuses (maxillary, ethmoid, frontal, and sphenoid) are sterile under normal conditions. Any one or all of them may become infected resulting in inflammation and edema of the pseudostratified epithelium that leads to an increase in tenacious secretions and the symptoms of acute sinusitis. The maxillary sinus is most commonly involved because its ostium is located at the highest part of the medial wall of the sinus. This leads to inadequate drainage and pooling of excess secretions, increased tenacity of secretions, and a drop in oxygen tension creating a more favorable environment for bacterial growth. Acute sinusitis occurs in all ages.

Infectious sinusitis may be bacterial, fungal, or viral. A large percent of acute sinusitis results from viral infection of the sinuses with or without bacterial superinfection. The latter is more symptomatic and patients are more likely to present to the physician. Episodes of sinusitis that occur all year round may be associated with allergies, polyps, or swimming.

The microbiology of acute bacterial sinusitis is similar to that of otitis media (Box 9-14). S pneumoniae and H influenzae account for > 50% of the sinusitis cases. Other pathogenic bacteria include M catarrhalis, a- and ß-hemolytic streptococci, S aureus, C pneumoniae, anaerobic bacteria, and occasionally gram-negative bacteria such as the Enterobacteriaceae or P aeruginosa. The ß-lactamase-producing H influenzae and M catarrhalis and intermediate or PRSP have proportionally increased in the microbiology of sinusitis and have important implications for management of sinusitis. Anaerobic bacteria, such as Peptostreptococcus, Fusobacterium, or Prevotella species, are implicated in ~ 8-10% of cases of acute sinusitis. These are usually polymicrobial and result from contiguous spread from the roots of the teeth.

Patients with craniofacial fractures have a higher incidence of sinusitis. P aeruginosa is a frequent cause of sinusitis in HIV-positive and in cystic fibrosis patients and must be considered in a patient who fails empirical antibiotic therapy that does not include antipseudomonal activity. S aureus is slightly more common in frontal or sphenoidal sinusitis. Fungi such as Aspergillus spp., Zygomycetes (Mucor spp.), and Pseudallescheria spp., among others, can occur in normal hosts or in immunocompromised hosts. Aspergillus sinusitis may occur in normal hosts or present as an allergic syndrome. Zygomycetes infection is more common in people with diabetes (particularly during acidosis), neutropenic patients, and patients on deferoxamine treatment. Viruses such as rhinovirus, influenza virus, adenovirus, coronavirus, and occasionally CMV, among others, account for sinusitis that presents with the primary rhinitis or upper respiratory tract infection syndrome. Coinfections of viruses and bacteria have a higher rate of prolonged duration of symptoms. Recurrent sinusitis may occur as a result of allergies, enlarged adenoids (especially in children), anatomic obstruction such as septal deviation, polyps, tumors, or craniofacial abnormalities, congenital primary or acquired immunodeficiency syndromes, or coexisting disease such as cystic fibrosis, asthma, or gastroesophageal reflux disease.

Chronic sinusitis, infection of the paranasal sinuses for 3 mo or more, may occur in patients with persistently impaired sinus drainage, immunodeficiency, or inadequately treated previous sinusitis episodes. The microbiology of chronic sinusitis is difficult to interpret with previous antibiotic use. However, chronic sinusitis is more often polymicrobial in etiology. There is a higher incidence of S aureus; anaerobes such as Peptostreptococcus, Fusobacterium, or Prevotella species (25-80%); gram-negative bacilli, such as P aeruginosa; and fungi in chronic sinusitis as compared with acute bacterial sinusitis.

Clinical Findings

A. Signs and Symptoms. The symptoms may vary with the severity, cause of the infection and presence of complications. Acute uncomplicated bacterial sinusitis presents with high fever, facial pain, headache, and nasal discharge predominantly. Nasal discharge or PND is purulent and may have a foul smell. Cough secondary to the PND may be present. A more common presentation is sinusitis associated with a viral upper respiratory tract infection. The course is usually milder and presents with "flulike" symptoms such as myalgias, rhinorrhea, and sore throat.

The symptoms of sinusitis may last longer than a viral syndrome and ~ 60% of these patients will have positive sinus cultures. Headache is common and may be frontal, temporal, vertex, or retro-orbital depending on the sinus involved. Sphenoidal sinusitis predominantly causes a vertex headache. Eustachian tube blockage caused by local edema and nasopharyngeal secretions may cause the sensation of "blocked ears." Patients may give a history of a predisposing condition such as sneezing or nasal itching with allergies. History of recurrent sinusitis or sinopulmonary disease, arthritis, and other organ disorders is important to identify immunodeficiencies and noninfectious etiologic diagnosis. Chronic sinusitis symptoms are occasional headaches, fatigue, irritability, low-grade temperature, facial pressure, and PND.

In acute uncomplicated bacterial sinusitis, there is severe tenderness overlying the affected sinuses. There may be swelling, erythema, and induration of the overlying area. Cloudy, yellow-to-green purulent drainage is noted. Intranasal examination should be conducted to attempt identifying the site of purulent discharge. Percussion examination of teeth should be done in patients with unilateral sinusitis or with a history of dental pain. Patients may have signs resulting from complications of sinusitis such as erythema, edema, and proptosis in orbital cellulitis. Purulent discharge and elevated temperature may be the only signs of acute sinusitis. Transillumination of the maxillary sinuses may demonstrate the presence of fluid.

B. Laboratory Findings. Acute sinusitis is usually associated with leukocytosis of > 10,000 cells/mm3. The sedimentation rate may be elevated. Cultures obtained by sinus puncture are regarded as the standard for an accurate microbiologic diagnosis and yield bacteria in ~ 60% of cases. Bacterial growth of > 105 colony-forming units (CFU)/mL suggests an etiologic role of those specific bacteria whereas growth of < 105 CFU/mL may represent contamination. Sinus puncture is recommended in patients who are severely ill; have intracranial or orbital complications, compromised immune systems, nosocomial sinusitis; or are not responding to standard empirical therapy. Newer endoscopic methods of collection of secretions are technically more difficult than puncture, especially from the maxillary antrum because of the location of its ostium. Endoscopic cultures obtained from the middle meatus may be contaminated with nasal secretions. In comparison with sinus puncture cultures, endoscopic cultures have a sensitivity of 65% and specificity of 40%, but this increases when evaluated specifically for S pneumoniae, H influenzae, and M catarrhalis.

C. Imaging. Standard radiography is useful for evaluating frontal and maxillary sinusitis with an anterior-posterior and Waters' view. Ethmoid sinuses are poorly seen on plain x-rays and difficult to interpret. Although standard radiography is less sensitive than CT, it may still be helpful in acute disease or determining bony erosion. The presence of air-fluid levels, opacification, and mucosal thickening is suggestive of acute disease. The coronal CT scan is a very sensitive imaging technique for sinus disease and is the imaging method of choice for accurate assessment. Findings on CT scan may include typical air-fluid levels that have a good correlation with acute bacterial sinusitis. Other findings such as membrane thickening, presence of polyps, and anatomic variations predisposing to or complicating sinusitis may help in defining the disease. Magnetic resonance imaging of the sinuses is also very sensitive in identifying mucosal disease. Both CT and magnetic resonance imaging are sensitive in detecting a fungus ball in the sinuses. Intracranial complications will require evaluation of the head with CT, especially if there are focal neurologic findings, or lumbar puncture for cell count, chemistry, and culture, and susceptibilities in a patient presenting with meningitis.

Differential Diagnosis

Patients with noninfectious sinusitis such as that related to Wegener's granulomatosis, tumors, or allergic rhinitis may present with signs and symptoms similar to those of infectious sinusitis.

Complications

The proximity of the orbits to the sinuses accounts for orbital complications. Orbital complications include periocular edema, orbital cellulitis, abscess, and further extension into the cavernous sinus leading to cavernous sinus thrombosis. Infection of the bone by direct spread or septic thrombophlebitis may occur. Frontal bone osteomyelitis and subperiosteal abscess cause a swelling and doughy feeling of the frontal bone called Pott's puffy tumor. Intracranial extension results in meningitis or epidural, subdural, or brain abscess. The incidence of these complications has declined, but they present as medical emergencies and require immediate attention. Cough or bronchitis from aspiration of postnasal drainage into the respiratory tract may also occur.

Treatment

Therapy of acute bacterial sinusitis includes symptomatic care along with an appropriate antibiotic regimen (Box 9-15). It may be helpful to stratify patients by the severity of symptoms. Patients who present with complicated sinusitis with evidence of intracranial or orbital extension should be hospitalized, undergo immediate appropriate diagnostic tests, and start on a parenteral empirical antibiotic regimen. Therapy should be guided by diagnostic sinus fluid aspiration. The recommended empirical antibiotic regimen in complicated sinusitis should include vancomycin, which is active against intermediate and highly PRSP, and a high-dose, third-generation cephalosporin (ie, cefotaxime or ceftriaxone) with activity against other usual pathogens. Empirical therapy should continue until culture and susceptibility results from sinus aspiration are available. Surgical consultations should be sought for possible drainage procedures. The increasing incidence of intermediate and highly PRSP and ß-lactamase-producing organisms has led to a decrease in the efficacy of amoxicillin for sinusitis.

Current recommendations for empirical antimicrobial therapy for acute uncomplicated bacterial sinusitis include amoxicillin/clavulanate or oral cephalosporins such as cefuroxime for 10 d. Other efficacious antibiotics include cefprozil, cefaclor, loracarbef, or cefpodoxime. TMP-SMX achieved 95% cure rates in older sinusitis studies; however, it is less effective against GAS and S pneumoniae.

Alternative antibiotics include macrolides such as clarithromycin (15 mg/kg/d for children, 500 mg every 12 h in adults) or azithromycin. Erythromycin has poor activity against H influenzae and is not recommended. Newer fluoroquinolones, such as levofloxacin or gatifloxacin (not approved for use in children and adolescents < 18 y old), have good activity against PRSP and are approved for use in adults with upper respiratory tract infections. TMP-SMX, cephalosporins or macrolides could be used for penicillin allergic patients. Odontogenic sinusitis treatment should include anaerobic coverage with either a ß-lactam/ß-lactamase inhibitor combination or the alternative regimen should include clindamycin or metronidazole. Fungal sinusitis requires aggressive surgical debridement along with parenteral or oral antifungal therapy.

Supportive measures for symptomatic relief may be considered. Decongestants provide symptomatic improvement by decreasing the nasal edema and obstruction. Oral decongestants are preferred over topical ones to avoid rebound vasodilatation. Steroid inhalers are not recommended unless the patient has significant allergy history and symptoms. Most symptoms will resolve in 7-10 d. Indiscriminate use of antibiotics is strongly discouraged to prevent the emergence of resistant strains of bacteria, particularly if the symptoms are consistent with a viral upper respiratory tract infection.

Persistent symptoms after an appropriate course of treatment may result from retained secretions, resistant or unusual organisms, presence of allergies, or possible immunodeficiency. Recurrent bacterial sinusitis should prompt further evaluation of the paranasal anatomy; immunoglobulin levels; neutrophil function analysis; HIV serology; sinus aspiration; and cultures for aerobic and anaerobic bacteria, fungi, and mycobacteria. Sinus aspiration and lavage or other drainage procedures may be more efficacious in relieving symptoms in these patients. Sinus aspirate should be sent for aerobic and anaerobic bacterial, mycobacterial and fungal culture, and susceptibilities. Patients with chronic sinusitis may require retreatment with a second course of broad-spectrum antibiotics to include antimicrobial activity against S aureus and anaerobes. This could be achieved with amoxicillin/clavulanate or combination therapy of a cephalosporin with clindamycin or metronidazole given for 4-6 wk. Occasionally antipseudomonal therapy may need to be added particularly in patients with cystic fibrosis, patients who are hospitalized, or patients who are HIV positive. Acute or chronic sinusitis exacerbations should be treated similarly to acute sinusitis.

Prognosis

Most community-acquired bacterial sinusitis episodes respond well to antimicrobial therapy. Complicated sinusitis or sinusitis in an immunocompromised host may require aggressive treatment including surgery. Such patients may continue to have recurrences and the attendant morbidity. Mortality in sinusitis is related mostly to complications such as meningitis.

Prevention & Control

Proper hygiene measures such as handwashing can reduce the incidence of acute sinusitis by decreasing transmission of infectious particles between persons (Box 9-16). Simple actions like covering the mouth with a handkerchief or tissue when sneezing or coughing can prevent aerosol or droplet transmission. Active immunization with pneumococcal polysaccharide vaccine or influenza vaccine may further decrease the incidence of these infections.

Read more...

OTITIS EXTERNA

Essentials of Diagnosis

• Infection and inflammation of the external auditory canal causing pain and itching, similar to infections of the skin and soft tissue.

• S aureus or group A Streptococcus often causes acute localized otitis externa, similar to furunculosis.

• Main symptoms are localized pain and itching.

• "Swimmer's ear" or acute diffuse otitis externa is often caused by P aeruginosa or by Aspergillus spp.

• Chronic otitis externa results from persistent drainage caused by chronic suppurative otitis media. This may present as chronic itching.

• "Malignant" otitis externa is a severe necrotizing P aeruginosa infection of the external auditory canal and adjacent tissues. Severe pain, tenderness, and other signs of complications may be present.

General Considerations

Inflammation of the EAC is particularly symptomatic because of the limited space for expansion of edematous tissue in the narrow external auditory canal.

Clinical Findings

A. Signs and Symptoms. Infection of the EAC is divided into four different categories (Box 9-12):

1. Acute localized otitis externa is the most common form of otitis externa. It is similar to staphylococcal infections of the skin and hair follicles. Because of limited area for expansion, inflammation and edema of the EAC wall cause intense pain and tenderness. The canal has local erythema, heat, and tenderness over the tragus. There may be associated preauricular lymphadenopathy.

2. Acute diffuse otitis externa or "swimmer's ear" is caused mainly by gram-negative organisms, particularly P aeruginosa. It occurs in hot, humid climates or may be associated with contaminated hot-tub baths. Fungal organisms such as Aspergillus spp. may also cause symptoms of pain and itching in the ear. The canal is erythematous, edematous, and, in some severe cases, hemorrhagic.

3. Chronic otitis externa is a complication of persistent chronic otitis media and resultant drainage into the EAC leading to chronic irritation. Itching of the EAC is the main symptom.

4. "Malignant" or invasive otitis externa is a severe, necrotizing infection of the EAC with invasion into the surrounding tissues including blood vessels, cartilage, and bone. P aeruginosa is the most frequently isolated organism. Immunocompromised hosts, elderly, and particularly diabetics are predisposed to this disease

B. Laboratory Findings. Laboratory findings are not helpful in the diagnosis and management of otitis externa. The white blood cell count and sedimentation rate may be elevated in malignant otitis externa. Cultures from the EAC or involved tissue in malignant otitis externa are frequently positive for P aeruginosa or other bacteria.

C. Imaging. Imaging is not required for otitis externa but CT or magnetic resonance imaging of the head delineates the extent of damage in malignant otitis externa and its complications. This could potentially aid in the further management of this condition.

Complications

Complications develop by local invasion such as temporal bone osteomyelitis, septic thrombophlebitis of the sigmoid or lateral sinus or jugular bulb, cranial nerve palsies, meningitis, or brain abscess.

Treatment

Gentle cleaning is recommended for most otitis externa. Local heat, topical antibiotic solutions such as neomycin, polymyxin, or ofloxacin, or systemic antibiotics, or some combination of these are effective in the treatment of acute otitis externa (Box 9-13). Irrigation with hypertonic (3%) saline and cleansing with alcohol and acetic acid mixed 1:1 are recommended for acute diffuse otitis externa, whether it is bacterial or fungal. Fungal otitis externa may also be amenable to treatment with m-cresyl acetate. Topical antibiotics combined with steroids are sometimes used for 1-2 d to decrease edema. Severe infections may require systemic antibiotics with activity against P aeruginosa. Malignant otitis externa may be treated with parenteral antipseudomonal antibiotics such as ceftazidime or penicillins with antipseudomonal activity such as piperacillin with aminoglycoside or oral antipseudomonal antibiotics such as the fluoroquinolones. Topical antipseudomonal antibiotics, such as neomycin, polymyxin, or ofloxacin, are used for 4-6 wk.

Read more...

OTITIS MEDIA

Essentials of Diagnosis

• Commonest cause of office visits in children between 6 mo and 2 y.

• Irritability, fever, earache, discharge from the ear, occasional vertigo.

• On otoscopic examination, the tympanic membrane is erythematous and has decreased mobility on pneumatic otoscopy, which demonstrates the presence of middle ear fluid.

• There may be diminished hearing.

• Laboratory values may show leukocytosis. Cultures of the ear are not routinely recommended.

General Considerations

Acute otitis media (AOM) is the middle ear inflammation that results in collection of fluid in the middle ear and associated local and systemic symptoms.

AOM is the most common reason for physician office visits for children under age 15 y. Children <> 6 children per room) centers, a sibling with AOM, parental smoking, and drinking from a bottle while lying flat on the back. Boys, Native Americans, and Alaskans have a higher incidence of AOM. A small percentage of children have an identifiable risk factor for recurrences such as congenital orofacial deformities and congenital or acquired immunodeficiencies such as HIV/AIDS. Recurrences occur in normal children with no apparent anatomic defects. A large percentage of AOM is viral, which may explain recurrences.

The most common bacterial organism responsible for otitis media is Streptococcus pneumoniae, which accounts for ~ 30-40% (Box 9-10) of cases. Cultures from the middle ear in various studies have demonstrated S pneumoniae, nontypable strains of H influenzae (21%), M catarrhalis (12%), S aureus, GAS (2-6%), and other less common gram-negative organisms including Pseudomonas aeruginosa. Penicillin-resistant S pneumoniae (PRSP) is increasing in the community and contributes to recalcitrant cases of AOM. PRSP is common in children < 6 y old, children who have received recent antibiotics, children with previous AOM, and children attending group daycare. Gram-negative organisms should be considered in neonates with AOM. Rare causes include M pneumoniae, which has a classic bullous lesion on the tympanic membrane, and Chlamydia trachomatis may be seen in very young infants. Occasionally mycobacterial or diphtheria middle-ear infections can occur.

Clinical Findings

A. Signs and Symptoms. Young infants or children may present with crying, irritability, anorexia, lethargy, or a history of pulling at the affected ear. Earache with or without associated drainage from the ear is the most common symptom in older children and adults. They may be febrile and occasionally present with vertigo, tinnitus, or decreased hearing.

Otoscopic examination reveals an erythematous tympanic membrane. The tympanic membrane may be bulging, retracted, or perforated and occasionally exuding purulent drainage from the perforation. Fluid in the middle ear is demonstrated by air-fluid levels, bulging, and decreased mobility of the tympanic membrane demonstrated by pneumatic otoscopy. Pneumatic otoscopy should be attempted in all children unless it is too painful. Other otologic techniques such as tympanometry and acoustic reflectometry can help assess the amount of fluid in the middle ear. Audiologic evaluation is necessary in children with hearing loss.

B. Laboratory Findings. Laboratory values are not helpful in the management of AOM. There may be polymorphonuclear leukocytosis. Routine middle ear cultures via tympanocentesis are not recommended unless the patient is toxic, has recurrent infections, or is not responding to empirical therapy. Swab cultures from the external auditory canal (EAC) do not accurately reflect the organism causing AOM because the EAC cannot be adequately decontaminated. Nasopharyngeal cultures are not specific in identifying the causative bacteria in AOM.

C. Imaging. Imaging is not of considerable help in otitis media. CT scans of the head should be done if mastoiditis or other complications are suspected.

Differential Diagnosis

Noninfectious causes of AOM, such as Wegener's granulomatosis, must be considered in a patient with recurrent and nonresponding disease. A foreign body in the EAC can present with earache and minimal erythema of the tympanic membrane. History and otoscopic visualization should identify a foreign body. A viral infection, fever, or crying or earwax removal can also cause a red tympanic membrane.

Complications

Chronic otitis media, effusion, mastoiditis, and intracranial extension may result from recurrent otitis media and persistent middle ear effusion. In the preantibiotic era, mastoiditis and intracranial extension occurred in ~ 20% and 2.5%, respectively, of AOM patients. Now that the use of antibiotics is common, these rates have decreased to 2.8% and 0.13%, respectively. Contiguous spread to the cranial fossae, temporal or petrous bone, or sigmoid or lateral sinuses results in suppurative complications. Conductive hearing loss because of chronic otitis media and effusion can potentially impair language development and academic functioning of the child.

Treatment

A large number of AOM cases are viral in nature with or without bacterial superinfection. Approximately 30% of AOM cases are bacterial. Studies have also demonstrated spontaneous resolution in 16% of S pneumoniae infections, 50% of H influenzae infections, and ~ 80% of M catarrhalis AOM, particularly in children older than 2 y. Because of concerns regarding suppurative complications, parental expectation, and perhaps convenience, antibiotic therapy has become the norm for most AOM treatment (Box 9-11). Numerous studies have now demonstrated that antibiotics benefit defervescence and otalgia, decrease suppurative complications, and improve tympanic membrane healing, but they have no significant benefit in long-term outcomes such as recurrence rates or chronic middle ear effusion. These studies and the recent increase in multi-drug-resistant organisms that have no or minimally efficacious treatment have brought this practice of judicious antibiotics use for AOM into question.

The approach to patients with AOM should be individualized. A delayed antibiotic approach can be considered in children older than 2 y with no immunodeficiency, no craniofacial anatomic abnormalities, intact tympanic membrane, and no previous AOM. The child should be scheduled for a follow-up visit. If a follow-up visit is not possible, an antibiotic can be started at the initial evaluation. The initial empirical antibiotic regimen should be active against the common organisms. Despite the emergence of resistance in these bacteria, amoxicillin is still the preferred and effective initial antibiotic of choice. In children with a history of antibiotic use in the preceding month, the initial antibiotic is still amoxicillin but given at a higher dose.

Antibiotics effective in the treatment of AOM include amoxicillin/clavulanate, cephalosporins such as cefaclor, cefixime, cefprozil, cefuroxime, cefpodoxime, loracarbef, or macrolides such as erythromycin, azithromycin, or clarithromycin, TMP-SMX, and erythromycin/sulfisoxazole (Pediazole). The newer expensive antibiotics do not have a significant benefit as first-line agents when compared with their cheaper counterparts (eg, amoxicillin and TMP-SMX). In patients with penicillin allergy, cephalosporins, macrolides, or TMP-SMX can be prescribed. Cephalosporins should be avoided in patients with histories of anaphylactic reaction to penicillin. Studies report mean clinical cure rates of 85-94% with amoxicillin.

Most patients start responding in 48-72 h. Causes for slower response or recurrence with lower-dose amoxicillin therapy include resistant organisms such as intermediate- or high-grade PRSP or ß-lactamase-producing H influenzae or M catarrhalis, suppurative complications, or noncompliance. Treatment failure is defined as lack of improvement in fever, ear pain, and persistent tympanic congestion, bulging, or otorrhea. It is important not to mistake a persistent middle ear effusion without signs of active infection as treatment failure. Treatment failure may be early (3 d) or late (10-25 d). If a child requires further treatment, high-dose (80 mg/kg/d) amoxicillin, a cephalosporin, amoxicillin/clavulanate, or a macrolide (either azithromycin or clarithromycin) may be prescribed. The choice of retreatment antibiotic depends on the risk of PRSP in the patient. Higher-dose amoxicillin or amoxicillin/clavulanate is still efficacious against intermediate-penicillin-susceptible S pneumoniae. Cefaclor and cefprozil are not good alternatives as second-line therapy because of their lower efficacy against nonsusceptible S pneumoniae and H influenzae. Because of the lack of activity against PRSP, clarithromycin, azithromycin, TMP/SMX, cefixime, ceftibuten, and loracarbef are recommended only as second-line antibiotics for patients at low risk for PRSP AOM.

Patients suspected of having PRSP AOM who fail high-dose amoxicillin should be considered for tympanocentesis for culture and susceptibilities. If empiric therapy is decided, the antimicrobial therapy should be effective against the ß-lactamase-producing H influenza and M catarrhalis in addition to being active against PRSP. Options include oral cefuroxime axetil, cefpodoxime or clindamycin, or parenteral cefotaxime, ceftriaxone or vancomycin. In children receiving clindamycin for PRSP, the addition of a ß-lactamase-stable cephalosporin may be required to cover for ß-lactamase-producing H influenzae. One parenteral dose of ceftriaxone 50 mg/kg/d is approved for AOM caused by susceptible S pneumoniae. However, ceftriaxone given daily for 3 d is likely to be more efficacious for AOM failing the first-line antimicrobial-agent therapy. Parenteral therapy is usually needed only for patients with severe AOM or those failing their second regimen. Middle ear aspirates should be sent for culture and susceptibilities to guide therapy in children failing second-line therapy. These patients should be reevaluated in 2 wk to ascertain that no suppurative complications have developed. A severely ill child failing initial therapy should be considered for admission and treatment with parenteral vancomycin and a third-generation cephalosporin, such as cefotaxime or ceftriaxone. A thorough evaluation for complications should also be conducted.

Symptomatic treatment is primarily pain control with analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs. On occasion, myringotomy (incision of the tympanic membrane) may be required to relieve the middle ear pressure. In most studies, myringotomy did not improve outcome even when combined with antibiotics. Antihistaminics and decongestants have equal efficacy as a placebo in AOM, and they are not recommended.

Treatment of recurrent otitis media includes prevention of recurrent attacks, a second course of antibiotics with broader antibacterial spectrum as mentioned above or specific treatment depending on middle ear cultures. Secondary antibiotic prophylaxis, surgical drainage or adenoidectomy, and active immunization are some of the measures used to prevent AOM. Children with three new episodes in 6 mo or four episodes in 1 y should be considered for antibiotic prophylaxis with amoxicillin or erythromycin/sulfisoxazole. Antibiotic prophylaxis decreases recurrences = 44%. The patient should be regularly evaluated for middle ear effusion. Middle ear effusion is seen in ~ 50% of children with AOM and usually resolves in 3 mo in the majority of patients. Persistent middle ear effusion or otitis media with effusion (OME) beyond 3-4 mo requires further management. Children with OME should have an audiologic test to detect any hearing loss. Patients with OME with normal hearing should be retreated with a 2- to 3-wk course of an antibiotic. If the effusion resolves, then a prophylactic antibiotic course of 3 mo may be of benefit to prevent recurrences. Children with OME and conductive hearing loss should be evaluated by an otorhinolaryngologist for surgical drainage procedures such as myringotomy and tympanostomy tubes (tubes placed in the tympanic membrane for permanent drainage).

Prognosis

Recurrent AOM or OME may impair hearing, language development, and learning capabilities of the patient. The prognosis is worsened in patients with intracranial extension of infection. Uncomplicated AOM resolves without significant sequelae.

Prevention & Control

Currently available 23 polyvalent pneumococcal polysaccharide vaccine produces poor immunologic responses in children <> 2 y . The Advisory Committee on Immunization Practices advises that this vaccine be given to children with higher likelihoods of pneumococcal infections such as HIV-positive, asplenic, or sickle cell anemia patients. Conjugated pneumococcal vaccine is available and is more efficacious in children < 2 y old and may contribute to lowering the incidence of pneumococcal otitis media.

Read more...

ACUTE EPIGLOTTITIS

Essentials of Diagnosis

• Occurs in children between 2 and 6 y , can occur in adults although it presents with less severity.

• Irritable, febrile, sore throat; odynophagia, dysphonia, and dyspnea.

• Sits forward drooling, toxic appearing, tachypneic

• Examination of the larynx should not be attempted. Direct examination should be performed only by a trained person and in a unit where immediate intubation or tracheotomy can be performed.

• Direct laryngoscopic examination reveals a "cherry red" edematous epiglottis.

• Polymorphonuclear leukocytosis is common. Blood and epiglottis cultures are often positive for Haemophilus influenzae type b, Staphylococcus aureus, or other bacteria.

General Considerations

Acute epiglottitis is a true respiratory emergency. An epiglottic infection leads to acute inflammation and edema of the epiglottis and can cause upper airway obstruction. Acute epiglottitis can occur at any age, however it is more common in children between 2-6 y and most often occurs in the winter and spring. Unlike croup, which is predominantly a viral disease, acute epiglottitis is a bacterial disease caused mainly by H influenzae type b, S aureus, or streptococcal species (Box 9-7). H influenzae type b was the most common organism isolated from children with acute epiglottitis, but widespread use of the H influenzae type b vaccine has dramatically decreased the incidence of H influenzae type b acute epiglottitis.

Clinical Findings

A. Signs and Symptoms. The child presents with a short (6- to 12-h) rapidly progressive febrile illness, sore throat, pain on swallowing, and shortness of breath. There is usually no antecedent history of a viral infection. Adults have a similar clinical presentation with sore throat being a predominant symptom.

The patient looks anxious, appears toxic, and assumes a forward-leaning, neck-extended posture. Drooling of oral secretions and muffled voice are the sine qua non. The child has marked tachypnea and may have an inspiratory stridor from the supraglottic mucosa prolapsing into the glottis. Lung auscultation may reveal crepitations or bronchial breath sounds if there is associated pneumonia.

B. Laboratory Findings. The white blood cell count is elevated with a polymorphonuclear reaction. The blood and epiglottis cultures are frequently positive. Bacteremia occurs in almost all of the children with H influenzae type b acute epiglottitis. Serum latex agglutination tests against H influenzae type b may be helpful in making a rapid microbiologic diagnosis in patients from whom cultures were not obtained before starting antibiotics.

C. Imaging. Caution must be exercised in sending these patients for tests or x-rays without adequate supervision and to avoid a delay in intubation. Radiographs of the neck show an enlarged edematous epiglottis with a normal subglottic space. Some x-rays may be negative or show subglottic obstruction, and the diagnosis may be obscured. (Figure 9-3). Chest x-rays may show evidence of pneumonia. Laryngoscopic evaluation should be carried out by trained personnel in a controlled setting such as an operating room or unit equipped for immediate intubation.

Differential Diagnosis

Croup or acute LTB presents with a clinical picture similar to that of acute epiglottitis. Croup has slower-onset, viral prodromal symptoms, a nontoxic appearing child, and absence of drooling. Anterior-posterior x-rays of the neck confirm the diagnosis. Other conditions that have a similar presentation include angioedema, foreign-body aspiration, and retropharyngeal or peritonsillar abscesses. Angioedema and foreign-body aspiration are suspected based on history and imaging or endoscopic evaluation. Radiographs or laryngoscopic evaluation identifies retropharyngeal or peritonsillar abscesses.

Complications

Mortality associated with untreated obstructive acute epiglottitis is ~80%. Respiratory failure from upper-airway obstruction is the most common complication. Occasionally patients will develop pulmonary edema along with the respiratory distress.

Treatment

Acute epiglottitis is a medical emergency. Once acute epiglottitis is suspected, the child should be kept in an upright position and be accompanied at all times by personnel trained in advanced cardiopulmonary life support. Diagnosis should be expeditiously established clinically or radiographically. Laryngoscopic examination should be attempted only in a unit equipped for immediate intubation and only by experienced personnel. Maintenance of a patent airway is of foremost importance in the care of a patient with acute epiglottitis. Patients with impending respiratory failure who cannot be intubated may require an emergency subglottic tracheotomy. All pediatric patients with acute epiglottitis should be intubated preferably via a nasotracheal or an uncuffed endotracheal tube. Observation alone is not recommended in pediatric patients because of high associated mortality. Management of adult patients depends on the severity of clinical symptoms and signs of upper-airway obstruction.

Blood and epiglottic cultures should be obtained once the airway is secured. Patients should be started on parenteral antibiotics that are active against H influenzae type b, S aureus, and streptococci (Box 9-8). Because of the high degree of ß-lactamase-mediated resistance in H influenzae type b, third-generation cephalosporins such as ceftriaxone or cefotaxime or a ß-lactam/ß-lactamase inhibitor combination antibiotic such as ampicillin/sulbactam should be started. Patients with acute epiglottitis usually improve within 12-48 h with appropriate antibiotics, and these should be continued orally or parenterally for 7-10 d. The average period of intubation is ~ 2 d, and direct visualization is the most effective way to determine time of extubation.

Prognosis

Expeditious diagnosis, immediate management of upper-airway obstruction, and institution of antibiotics decreases morbidity and mortality related to acute epiglottitis. Full recovery without sequelae is expected in such patients.

Prevention & Control

H influenzae type b polysaccharide vaccination can further decrease the incidence of acute epiglottitis (Box 9-9). However, patients can still be susceptible to non-type-b H influenzae and other bacterial etiologies of epiglottitis.

The secondary attack rate of H influenzae type b among all household contacts, especially in children < 4 y old, can be decreased by a prophylactic 4-d course of rifampin (20 mg/kg/d in a single daily dose). Rifampin prophylaxis should be given to the patient and all household contacts regardless of previous immunization status, to prevent carriage state.

Read more...

ACUTE LARYNGOTRACHEOBRONCHITIS (CROUP)

Essentials of Diagnosis

• Most often in children ages 6 mo to 6 y, peak is at 2 y.

• Fever, hoarseness of voice followed by paroxysms of nonproductive, brassy cough that ends with a characteristic inspiratory stridor.

• The child appears anxious and has tachypnea, inspiratory stridor, retraction of intercostal muscles, and associated rhonchi or wheezing.

• Anterior-posterior x-ray view of the neck shows the subglottic obstruction.

• Microbiologic diagnosis can be established by serology, viral or bacterial cultures from the pharynx, or rapid antigen detection enzyme immunosorbent assays such as for RSV or influenza type A.

General Considerations

Acute laryngotracheobronchitis (LTB) or croup is subglottic inflammation and edema caused by a viral or bacterial infection of the larynx, trachea, and bronchi (Box 9-5). Croup is the most common cause of upper respiratory tract obstruction in children between the ages of 6 mo and 6 y, with the peak occurrence at 2 y old. It is caused mostly by viruses, primarily parainfluenza virus types I and II, although others, such as influenza type A or B, RSV, and adenovirus are also implicated. Occasionally M pneumoniae can cause LTB.

Clinical Findings

A. Signs and Symptoms. Most children have hoarseness of voice and a brassy cough with an associated inspiratory or even an expiratory stridor. Fever, rhinorrhea, sore throat, and cough usually precede this. Symptoms may vary in intensity and last ~ 3-4 d if mild. Patients appear apprehensive and tend to lean forward. The child may have tachypnea and might be using accessory respiratory muscles. Inspiratory or expiratory stridor is prominent. Pulmonary examination may reveal rhonchi, crepitations, or wheezing. Breath sounds may be diminished if upper airway obstruction is severe and air entry is greatly decreased.

B. Laboratory Findings. The white blood cell count may be normal or mildly elevated. Noninvasive pulse oximetry to monitor the oxygen saturation is recommended. Arterial blood gas assessment shows hypoxemia and/or hypercapnia, depending on the severity of the disease.

C. Imaging. Lateral neck x-rays show overdistended hypopharynx, subglottic narrowing that is wider on expiration than inspiration, thickened vocal cords, and a normal epiglottis. Anterior-posterior views of the neck show edematous subglottic walls converging to create a characteristic "steeple sign" (Figure 9-1). There may also be diffuse narrowing of the trachea and bronchi (Figure 9-2).

Differential Diagnosis

Acute epiglottitis is a major differential diagnosis to be considered when a child presents with these symptoms. Radiographs of the neck can easily help differentiate the two conditions. Other causes of similar symptoms include foreign-body aspiration, which can be determined by history, x-rays, or endoscopic evaluation. Membranous croup or bacterial tracheitis should also be considered if the child presents with a clinical picture similar to croup but appears more toxic and has subglottic narrowing on radiographs of the neck.

Complications

Severe croup, as may occur with influenza type A, may require tracheotomy or intubation in = 13% of patients and have an associated mortality of 0-2.7%. A small percentage of children with prolonged intubation or severe disease may develop subglottic stenosis. A few follow-up studies have shown an increase in hyperactive airways in children with a history of croup.

Treatment

Antibiotics are not routinely recommended for the treatment of croup unless the patient has symptoms or cultures suggestive of bacterial etiology (Box 9-6). Cool air humidification and supportive care are essential to keep the child calm, to prevent further tachypnea and distress. Respiratory rate is the best predictor of hypoxemia. Noninvasive pulse oximetry or arterial blood gas testing for PaO2 or PaCO2 should aid in assessment of the patient's condition and response to therapy. Noninvasive monitoring is preferred to prevent further anxiety in the child.

Nebulized racemic epinephrine is important in the therapy for croup because the a and ß agonists decrease edema and relieve obstruction by vasoconstriction. Racemic epinephrine nebulization is well tolerated, even by the younger children, and may decrease the need for intubation. Children receiving racemic epinephrine should be observed for relapse because epinephrine has a short half-life and rebound vasodilatation and edema can occur. Racemic epinephrine nebulization should be used cautiously in children with left ventricular outflow tract obstruction such as tetralogy of Fallot or idiopathic hypertrophic subaortic stenosis. In severe croup, corticosteroids (eg, dexamethasone) decrease subglottic edema, the number of racemic epinephrine treatments, and intubations.

Some children will fail medical management and require intubation. Intubation should be done in fully equipped units and preferably via the nasotracheal route. Extubation is usually attempted in ~ 5-7 d if extubation criteria are met. Extubation criteria include decreased secretions, decreased leakage around the endotracheal tube (which indicates decreased edema), and an alert child. Failure to extubate should prompt further endoscopic evaluation.

Prognosis

Croup is mostly a self-limited disease with complete uncomplicated resolution. As mentioned above, some children may develop hyperactive airways or become predisposed to recurrent croup. A few may develop subglottic stenosis caused by severe disease or prolonged intubation.

Prevention & Control

Good handwashing and cleanliness can help decrease transmission from an infected patient, particularly at daycare centers or even in the home environment.

Read more...

ACUTE LARYNGITIS

Essentials of Diagnosis

• Hoarseness or loss of voice (aphonia).

• Associated symptoms of rhinitis, pharyngitis, or cough.

• Children tend to develop airway obstruction.

• On direct examination, the larynx is hyperemic and edematous, with or without ulcerations.

• Mostly viral, occasionally bacterial.

• Persistent hoarseness lasting > 10 d should prompt laryngoscopy to exclude other etiologies.

General Considerations

Laryngitis is the infection of the larynx that results in an inflammatory reaction and consequential symptoms and signs. Common cold viruses such as rhinovirus, influenza virus, adenoviruses, RSV, or parainfluenza viruses may cause acute laryngitis. It usually presents in winter as part of an upper respiratory tract infectious syndrome. Bacterial laryngitis is less common and is caused mainly by S pyogenes or Moraxella catarrhalis. Rarely laryngitis may be caused by Mycobacterium tuberculosis, syphilis, or fungi such as Histoplasma capsulatum, Blastomyces dermatiditis, or Candida albicans.

Clinical Findings

A. Signs and Symptoms. Hoarseness, aphonia, and symptoms of associated upper respiratory tract infection such as rhinitis or pharyngitis may accompany acute laryngitis. Respiratory obstruction may occur particularly in children. Direct examination when done shows the larynx to be hyperemic and edematous, with or without ulcerations. An exudate or membrane may be seen in diphtheria, streptococcal, or EBV laryngitis.

B. Imaging. Lateral x-ray of the neck may be helpful to exclude acute bacterial epiglottitis or bacterial tracheitis. If symptoms of hoarseness persist beyond 2 wk, patients should be evaluated by direct visualization of the larynx by laryngoscopy.

Differential Diagnosis

Voice abuse is the most frequent noninfectious cause of hoarseness. Differential diagnosis includes tumors, paralysis of the vocal cords, chemical irritants, or gastroesophageal reflux. Patients with laryngitis must also be differentiated from those with acute epiglottitis or bacterial tracheitis, which usually present with more systemic symptoms.

Complications

Respiratory obstruction in children is the most serious complication.

Treatment

Because the majority of laryngeal infections are viral, therapy is mostly supportive with voice rest, warm saline gargles, and increased humidity. If specific microbiologic diagnosis is made with positive microbiologic cultures, then therapy should be directed at the organism isolated.

Prognosis

Long-term prognosis is excellent with no residual symptoms.

Prevention & Control

Preventive measures for laryngitis are similar to those for common cold and pharyngitis.

Read more...

PHARYNGITIS

Essentials of Diagnosis

• Pharyngeal discomfort or pain, pain on swallowing (odynophagia).

• Associated symptoms such as myalgia, fever, rhinorrhea, and lymphadenopathy depend on the etiologic agent.

• Pharyngeal erythema with or without exudate or lymphadenopathy.

• Leukocytosis, GAS RADT, and bacterial culture or other serologies may provide the definitive microbiologic diagnosis.

General Considerations

Pharyngitis is an acute infection of the pharyngeal mucosa caused by a variety of pathogenic microorganisms, the majority of which are viral (Box 9-2). A minority of pharyngitis episodes are bacterial and, of those, group A streptococcus is the most common cause. Viral pharyngitis is caused by respiratory viruses such as rhinoviruses, coronaviruses, adenoviruses, influenza, and EBV. Bacteria causing pharyngitis include group A and non-group A streptococci, Corynebacterium diphtheria, Corynebacterium pseudodiphtherium, Neisseria gonorrhoeae, Yersinia enterocolitica, Arcanobacterium hemolyticum, and anaerobic bacterial species. Persons infected with the human immunodeficiency virus (HIV) may present with an HIV-induced exudative pharyngitis during the acute retroviral syndrome or with Candida-induced pharyngitis. The etiology of pharyngitis remains obscure in 40% of cases. Most pharyngitis occurs as result of respiratory or contact transmission; few cases are foodborne. Outbreaks are common in winter or in crowded living situations, especially in families with children who serve as reservoirs by acquiring infections in daycare centers or school.

Clinical Findings

A. Signs and Symptoms. The severity of the pharyngitis may vary from mild to life threatening depending on the etiologic agent. Symptoms of mild pharyngitis are irritation or sore throat. With increasing severity there may be severe pain that increases on swallowing or talking, plus cervical lymphadenopathy with or without fever. Pharyngitis can be life threatening with inflammatory edema of pharyngeal walls and extension to the larynx leading to respiratory distress.

An erythematous pharynx with or without exudates or cervical lymphadenopathy is the common finding on examination. Because it impacts therapeutic decision-making, it is important to attempt clinical differentiation between viral and bacterial pharyngitis. However, this may be difficult. Associated clinical signs and symptoms provide diagnostic clues to formulate a differential diagnosis. Mild pharyngeal symptoms with rhinorrhea usually suggest a viral etiology. Pharyngeal exudates suggest streptococcal pharyngitis, HIV, or EBV. Presence of vesicles and ulcers is seen with herpes simplex and coxsackievirus. Coxsackievirus-related vesicles often occur on the hard palate. Adenoviral pharyngitis is associated with conjunctival congestion. EBV, HIV, A hemolyticum, and streptococcal toxic shock can present with pharyngitis and a generalized rash. Pharyngitis with elevated transaminases, splenomegaly, and atypical lymphocytosis is the typical manifestation of EBV-induced infectious mononucleosis. Aseptic meningitis along with pharyngitis should suggest an acute HIV or enteroviral syndrome. Systemic viral infections with CMV, measles, and rubella, among others, can present with acute pharyngitis.

Sore throat with cough and signs of pneumonia may suggest influenza, Chlamydia pneumoniae or Mycoplasma pneumoniae. Diphtherial pharyngitis is associated with a grayish pseudomembrane.

GAS (Streptococcus pyogenes) pharyngitis frequently presents with fever of > 38.3 oC, chills, sudden-onset sore throat, painful and difficult swallowing, and tender cervical lymph nodes. Lymphadenopathy is more likely to be anterior and tender in GAS pharyngitis, unlike viral pharyngitis, which is more likely to be generalized and nontender. Exudate with intense pharyngeal and tonsillar pillars erythema is seen. Occasionally patients, especially children, present with systemic symptoms of nausea, vomiting, and headache. Symptoms of non-group A, such as group C or G, streptococcal pharyngitis are very similar to GAS and clinically indistinguishable. These symptoms and signs are nonspecific for GAS pharyngitis. However, absence of fever or presence of other symptoms such as rhinorrhea, cough, oral ulcers, and viral exanthema strongly suggests a viral rather than a GAS pharyngitis.

B. Laboratory Findings. Laboratory values may not be of considerable help. Testing for GAS should be done in all patients in whom GAS pharyngitis cannot be confidently excluded on clinical grounds. Diagnosis of GAS pharyngitis can be made by RADT, which has a sensitivity of 80-95% and specificity of 95%. Use of RADT significantly increases the number of patients receiving appropriate antibiotic treatment. Because of its relatively lower sensitivity, a negative test should be confirmed with a throat culture. Throat cultures taken from the tonsillar fossae and posterior pharyngeal wall are 90-95% sensitive for the diagnosis of GAS pharyngitis. Follow-up cultures are not generally recommended except in patients with histories of acute rheumatic fever or poststreptococcal glomerulonephritis or in outbreaks. Asymptomatic contacts of the patient do not need to be screened unless there is an outbreak or the patient has a history of acute rheumatic fever.

Special culture media for N gonorrhoeae or C diphtheria should be specifically requested when these bacteria are suspected. Serologic testing can establish the diagnosis of EBV, HIV, CMV, influenza, M pneumoniae, and C pneumoniae. During acute HIV retroviral syndrome, HIV RNA polymerase chain reaction, or HIV culture can help make a diagnosis because HIV serology may be negative.

C. Imaging. A lateral neck x-ray should be done if the patient has associated symptoms of stridor or respiratory compromise, to rule out laryngeal obstruction.

Differential Diagnosis

In children, Kawasaki's syndrome can present with a clinical picture similar to an infectious pharyngitis. Noninfectious causes of pharyngitis include chemotherapy-induced mucositis, drug reactions, agranulocytosis, or connective-tissue disorders.

Complications

Local complications of bacterial pharyngitis include peritonsillar or retropharyngeal abscesses or Fusobacterium necrophorum jugular vein thrombophlebitis and its embolic complications (Lemeire's syndrome). In the United States, appropriate and timely antibiotics have decreased nonsuppurative complications of S pyogenes such as rheumatic heart disease or poststreptococcal glomerulonephritis. C diphtheria pharyngitis may become complicated by acute upper-airway obstruction, myocarditis, or neuritis. Viral pharyngitis may be complicated by secondary bacterial infection of the sinuses or lower respiratory tract.

Treatment

In patients with a clinical picture consistent with GAS pharyngitis, empirical therapy should be started to prevent suppurative and nonsuppurative complications, to decrease infectivity and transmissibility, and to induce clinical improvement of symptoms (Box 9-3). Patients with a high index of suspicion for GAS pharyngitis but negative or pending RADT/culture results can be given empirical antibiotics until the results are available. An alternative approach is to withhold antibiotics until the culture is positive for S pyogenes. Delaying therapy against GAS does not increase the incidence of rheumatic heart disease or recurrences with the same strain of S pyogenes. Following the latter course will decrease inappropriate antibiotic use and control the increase in antibiotic resistance.

Antibiotic selection is based on efficacy, ease of administration, cost, compliance, and spectrum of the antibiotic. The treatment of choice is penicillin V or amoxicillin for 10 d to treat and eradicate carriage. Intramuscular benzathine penicillin G may be given in patients unlikely to complete a 10-d course. Shorter courses are not recommended until more definitive studies are available. Erythromycin or other macrolides (such as clarithromycin or azithromycin), or oral cephalosporins are the recommended alternatives for bacterial pharyngitis in patients who are allergic to penicillin. Absence of penicillin-resistant GAS and limited (5%) resistance to erythromycin make it imperative to choose a cheaper alternative to the newer more expensive antibiotics. In some patients with recurrent GAS pharyngitis, penicillin is unable to eradicate nasopharyngeal carriage. In such patients, rifampin, clindamycin, or amoxicillin/clavulanate use may decrease colonization. Patients with negative throat RADT/cultures should have antibiotics discontinued.

Pharyngitis caused by anaerobic bacteria may respond to penicillins, amoxicillin/clavulanate, or clindamycin. A hemolyticum is susceptible to erythromycin. Yersinia pharyngitis requires treatment with a third-generation cephalosporin, an aminoglycoside or trimethoprim-sulfamethoxazole (TMP-SMX). Effective therapies for gonococcal pharyngitis include ceftriaxone, cefixime, or fluoroquinolones such as norfloxacin, ofloxacin, or ciprofloxacin. Treatment of choice for Mycoplasma pharyngitis is either doxycycline or macrolides. Doxycycline is contraindicated in children < 8 y old because it causes discoloration of teeth.

Symptomatic oropharyngeal herpes simplex ulcers, particularly in an immunocompromised host, should be treated with acyclovir for 7-10 d. Influenza type A pharyngitis can be treated with amantadine or rimantadine or the neuraminidase inhibitors if the patient presents within 48-72 h of onset of symptoms. HIV acute retroviral syndrome should be considered for treatment with combination antiretroviral therapy.

General measures for symptomatic relief include fluids, warm saline gargles, and nonsteroidal anti-inflammatory drugs. Aspirin should be avoided in children with viral infections, particularly varicella-zoster virus infection, to prevent Reye's syndrome. Patients that appear toxic or patients with suppurative complications should be hospitalized for parenteral or surgical management.

Prognosis

Uncomplicated pharyngitis results in no sequelae. Prognosis of GAS pharyngitis complicated by rheumatic heart disease or poststreptococcal glomerulonephritis is good with penicillin prophylaxis in rheumatic heart disease and spontaneous remission in poststreptococcal glomerulonephritis. Suppurative complications have minimal long-term adverse effects.

Prevention & Control

Active immunization plays a role in prevention with regard to diphtheria and influenza types A and B (Box 9-4). Tonsillectomy is recommended in selected patients. Penicillin prophylaxis is required in patients at risk for recurrent rheumatic fever.

Read more...

THE COMMON COLD

Essentials of Diagnosis

• Acute rhinorrhea, sneezing, sore throat, burning eyes, cough, malaise, headache, anosmia.

• Usually there is no or low-grade fever in adults, higher fever in infants and children.

• Examination may demonstrate serous nasal discharge, conjunctival and/or pharyngeal congestion, and rhonchi.

• Diagnosis is made clinically, can be confirmed by serology or nasopharyngeal viral cultures in selected cases.

• Imaging is helpful if bacterial superinfective complications suspected (ie, sinusitis).

General Considerations

A "cold" is a self-limited viral infection of the upper respiratory tract presenting with a coryzal syndrome. It is the most common cause for physician visits and absenteeism in school and industry. Infection rates increase sharply during the fall through spring months with peak activity being in the winter. During these months, adults and children have an average of 2-4 and 6-8 colds per year, respectively.

Rhinoviruses are the most common cause of colds, accounting for one third of all colds (Box 9-1). Parainfluenza 1-4 viruses, coronaviruses, influenza types A and B, adenovirus, respiratory syncytial virus (RSV), and their numerous serotypes also are predominant viruses that induce colds. These viruses share a common property of frequent antigenic variation and evasion from the host humoral defense mechanisms, thereby permitting their persistent survival in the community. Other viruses can present with coldlike symptoms during the prodromal period, but their primary syndrome may be localized to another organ system(s).

Transmission is via aerosol, droplet, or direct contact with infected saliva or fomite from an infected person. The rate of infection increases in families with school-age children and in overcrowded and poorly ventilated living spaces. Cigarette smokers are more likely to develop severe disease as compared with nonsmokers.

Once the virus enters the cell, replication and subsequent shedding of the virus occur. The cytopathic effect of the virus on the epithelium varies depending on the virus, being relatively mild in rhinovirus and more marked with influenza virus infection. There is an acute inflammatory response, increased vascular permeability, tissue edema, mucus production, and serum transudation, resulting in the typical cold symptoms of rhinorrhea, nasal obstruction, and cough. After the initial neutrophilic response, there is immunoglobulin M (IgM), IgG antibody, and cytokine production such as interferon, tumor necrosis factor-a, interleukin 8, interleukin 6, and others. Cytolytic T-cell response is more marked and significant in the immune response against influenza viruses than rhinoviruses. Antibody neutralization is the predominant immune mechanism for the latter. Production of antibodies coincides with the cessation of viral replication and waning of the inflammatory response and symptoms. This period may vary depending on the infecting virus. Viral shedding may occur for a few days to weeks.

Clinical Findings

A. Signs and Symptoms. Onset of symptoms is between 24 and 72 h after the infectious contact. Symptoms include malaise, rapid progression to serous nasal discharge and obstruction, sneezing, throat irritation, and cough. There may be nasal intonation of voice with nasal obstruction or hoarseness with laryngeal involvement, or both. Patients may complain of burning of the eyes. Fever usually is low-grade or absent in adults but can be much higher in infants and children. Loss of smell and taste occurs as a result of nasal mucosal edema and obstruction. Overall, the symptoms can last for 1-2 wk.

Associated clinical findings can suggest a specific viral diagnosis; for example, the presence of conjunctivitis suggests an adenoviral upper respiratory infection; myalgias and lower respiratory symptoms such as pneumonia or bronchiolitis may suggest an influenza or RSV infection. Mild disease suggests rhinovirus or coronaviruses. Symptoms of complications such as sinusitis, otitis media, or lower respiratory tract infection may be present. Patients with previous hyperactive airways or asthma can develop exacerbations.

The patient usually appears tired, with thin serous nasal discharge, mild tenderness over the sinuses, and mildly suffused conjunctiva without frank conjunctivitis, and the skin over the nostrils may be red from recurrent blowing of the nose. Pharyngeal erythema without any exudates or lymphadenopathy may be present. Lung examination may reveal evidence of bronchitis or bronchiolitis.

B. Laboratory Findings. Most colds are diagnosed clinically and do not need any further investigations. Mild leukocytosis or leukopenia with or without thrombocytopenia may be noted. Serologies and viral cultures can make a specific viral diagnosis; however, this should be attempted only in selected cases. Rapid RSV or influenza type A antigen detection enzyme immunoassays are very sensitive for nasopharyngeal specimens. Influenza, parainfluenza, adenovirus, cytomegalovirus (CMV), and other viruses can be isolated on cell line cultures. Serologies are available for influenza, parainfluenza, RSV, adenovirus, CMV, and Epstein-Barr virus (EBV). The serologic test is considered positive for active infection if an IgM is present during acute infection or a fourfold rise in IgG in paired sera is detected. Patients with equivocal histories for colds versus group A streptococcal (GAS) pharyngitis should have a rapid antigen detection test (RADT) and bacterial cultures for group A streptococcus.

C. Imaging. No imaging is recommended for uncomplicated colds. However if bacterial or viral complications such as sinusitis or pneumonia are suspected, then appropriate radiographs should be done. A computed-tomography (CT) scan study in patients with a common cold shows frequent involvement of the sinuses.

Differential Diagnosis

A common dilemma is clinically differentiating the common cold from GAS pharyngitis and prodromal symptoms related to systemic syndromes caused by other viruses such as measles, chickenpox, EBV, or CMV. The presence of high fever, chills, severe pharyngeal congestion with exudate, and tender lymphadenopathy is more likely to suggest GAS pharyngitis. An RADT and bacterial culture may be able to confirm this. An exposure history to chickenpox or other viral disease may be a helpful clue to the correct diagnosis. A diagnosis of allergies is evident with rapid resolution and no recurrences in the absence of exposure.

Complications

A complication of the common cold is viral or bacterial sinusitis. A common cold CT scan study by Gwaltney et al (1994) showed that sinus involvement occurs in > 60% of patients with a cold, with 79% of these resolving spontaneously in 2 wk without antibiotics. However, bacterial superinfections of the sinuses, middle ear, or both are potential complications. Viral pneumonia or worsening of bronchospastic airway disease is seen, particularly in children or immunocompromised hosts.

Treatment

The old idiom of "prevention is better than cure" is certainly true for the treatment of the common cold. Multiple different viruses, their many serotypes, and rapid mutations pose a considerable challenge in the development of one vaccine or drug for cold prevention or treatment. Symptomatic support is the only therapy because no effective antiviral therapy is available.

Treatment is directed to rhinorrhea, nasal obstruction, sore throat, and cough. Sneezing, rhinorrhea, and nasal blockage improve markedly with topical or systemic decongestants that decrease edema by vasoconstriction. Topical decongestants such as phenylephrine (0.5% or 0.25%) or ephedrine (1%) nasal spray or drops should be used for a short period. Rebound congestion particularly with use of decongestant sprays beyond 3-4 d can occur. Systemic decongestants include pseudoephedrine hydrochloride, ephedrine, phenylephrine hydrochloride, propylhexedrine hydrochloride, phenylpropanolamine hydrochloride, xylometazoline hydrochloride, oxymetazoline hydrochloride, naphazoline hydrochloride, and tramazoline hydrochloride. Decongestant side effects include tachycardia, elevated blood pressure, fatigue, and dizziness. These should be used cautiously in patients with hypertension and dysrhythmias.

Nasal anticholinergics are effective in inhibiting the parasympathetic activation that contributes to rhinorrhea. Ipratropium bromide nasal spray reduces rhinorrhea and sneezing in the first 3 d of the cold.

Antitussives such as codeine, dextromethorphan, hydrocodone bitartrate, and diphenhydramine hydrochloride suppress the cough reflex in the medullary cough center. Analgesics can be used to improve the myalgias, headache, and sore throat that accompany the common cold. Antihistaminics have no role in the treatment of common cold. The majority of the above mentioned drugs are available over the counter in combination with antihistaminics, analgesics, or antitussives.

Nonspecific measures such as warm saline gargles are encouraged. The role of vitamin C in the common cold is controversial. Studies with dosages of 1-30 g/d demonstrate a 5-29% decrease in severity and duration of symptoms. However, these studies had significant variations for conclusive evidence. Similarly, despite numerous studies of the role of zinc in the management of cold, zinc's role is still controversial and needs further confirmation. Antibiotics have no role in colds unless patients have evidence of bacterial superinfection of the upper respiratory tract.

Prevention & Control

Handwashing is key in the prevention of common colds. Minimizing aerosol or droplet transmission with tissues or covering the mouth should be taught to children and adults. Experimental therapies with interferon-a2 and leukocyte A interferon show some role in the prevention of cold. Producing vaccines for these viruses is difficult because of their numerous serotypes. However, active vaccination can be used for influenza types A and B along with the prophylactic use of amantadine or rimantadine.

Read more...

INFECTIOUS DISORDERS WITH DYSPHAGIA & DYSARTHRIA AS DOMINANT FEATURES

Introduction

Involvement of cranial nerves nine through twelve is less frequent in meningeal infections, perhaps because their dysfunctions are less obvious, and they are less carefully examined. Involvement of their nuclei in the brainstem is, however, common in polio, leading to severe dysphagia, dysarthria, and respiratory difficulties. Thus, polio must be considered in unvaccinated individuals who have traveled abroad.

Botulism & Pseudobotulism

Although botulism is a disorder of the neuromuscular junction rather than peripheral nerves, patients with botulism commonly present with dry mouth, dysarthria, dysphagia, diplopia, and impaired ocular accommodation. Rapid recognition of this disease is important. Prompt administration of antitoxin along with ventilatory support is essential in the management of botulism. In addition, recognition of the disease should prompt an intensive search for contaminated foodstuffs, which are most often the cause of the condition in adults. Victims who have only early symptoms may be recognized only because they were identified as sharing certain foodstuffs with individuals who have clear-cut disease.

A cluster of signs and symptoms similar to those in botulism may occur after ingestion of any part of the plant, Jimson weed (Datura stramonium); the syndrome may mimic botulism in patients who present with dysphagia; dilated, fixed pupils; and dry mouth (pseudobotulism), which is often accompanied by visual or auditory hallucinations. The Datura plant contains the anticholinergics atropine and scopolamine, which are highly concentrated in the seeds and can cause serious illness or death. Teenagers seeking mind-altering experiences sometimes experiment with Datura, only to die, probably from the cardiotoxic principle in the plant. They usually present with the pseudobotulism syndrome (fixed, dilated pupils and dry mouth), which is distinguishable from true botulism primarily by the history of contact with the Datura plant or its seeds and by the hallucinations, which are not a feature of true botulism. If the cardiovascular system is stable, the patients usually improve over time without therapy, other than emptying the stomach, using activated charcoal, or both; however, if the patients manifest profound toxicity, including bradycardia or tachycardia, the use of the antidote physostigmine should be considered.

Datura poisoning might also suggest rabies to the initial observer, if the hallucinations are mistaken for encephalopathy and if the dysphagia is mistaken for hydrophobia.

Rabies

Rabies should also be considered in the differential diagnosis of patients presenting with dysphagia and dysarthria, with or without hydrophobia and laryngeal spasms. Rabies must be considered in any patient who has traveled to third-world countries and who has had any contact with potentially infected animals. Skunks, raccoons, and bats are the main animal reservoirs of rabies in the United States.

Treatment with human immune globulin and diploid cell-derived vaccine is very effective for individuals exposed to or bitten by rabid animals, but it is ineffective once neurological symptoms have developed. It is important for persons in close contact with the victims, whose body fluids may be infectious or for others who have had contact with the same or other infected animals to receive postexposure prophylaxis. A detailed review of the indications and procedures for postexposure prophylaxis has been provided by the Centers for Disease Control and Prevention (CDC/MMWR, 1999).

Read more...

INFECTIOUS DISORDERS INVOLVING CRANIAL NERVES

Essentials of Diagnosis

• History: antecedent meningeal infection; infections of paranasal sinuses or skull base.

• Signs: cranial nerve deficits, especially nerves two, four, five, six, and seven.

• Laboratory: evidence of meningeal infection in CSF studies; MRI imaging of skull base and paranasal sinuses showing signs of an inflammatory process.

Involvement of the cranial nerves by infectious processes is usually the result of infection in the subarachnoid space at the base of the brain or in structures at the base near or through which cranial nerves course (eg, the cavernous sinus, as discussed previously). In the differential diagnosis, one must be aware that cranial nerves are also commonly involved by neoplastic processes, by inflammatory processes of other types (eg, sarcoidosis), or by vasculitic diseases, especially those affecting medium and small size vessels (eg, giant cell arteritis, polyarteritis nodosa, and diabetes mellitus).

Involvement of cranial nerves three, four, and six and the first division of five can be seen together because they traverse the cavernous sinus. Thus infections or infective thrombosis in the cavernous sinus can involve these nerves together.

Any meningeal infection, particularly if prolonged, can involve the cranial nerves at the base of the brain, so that palsies, particularly of the third, sixth, seventh, and eighth cranial nerves, can be seen in the course of pyogenic meningitis of any type or in more slowly evolving meningitides caused by tuberculosis, fungal infections, syphilis, or Lyme disease. Lyme disease seems to have a particular affinity for the seventh nerve; unilateral or bilateral facial paralysis is commonly seen. Involvement of the fifth nerve can be seen from reactivation of varicella-zoster virus in the trigeminal ganglion producing the well-known shingles eruption in one or more divisions of the nerve. Involvement of the intracranial portion of the carotid artery may occur in the course of ophthalmic zoster with thrombosis of the vessel and a middle cerebral distribution stroke. In contrast, reactivation of HSV in the same ganglion usually results only in the production of fever blisters on the lip.

The common Bell's palsy involving the facial nerve is tenuously associated with herpes simplex infections, prompting some authorities to recommend treatment of such cases with acyclovir. Involvement of the facial nerve by varicella results in the Ramsey-Hunt syndrome, with the appearance of vesicles in the ear. The facial nerve is susceptible to a variety of infections; in addition to those mentioned above, it is vulnerable to bacterial infections in the petrous apex. It, along with the eighth nerve, can be involved in Pseudomonas infections of the ear in diabetics (malignant external otitis).

Read more...

INFECTIOUS DISORDERS WITH FOCAL DISTURBANCES AS A DOMINANT FEATURE

Essentials of Diagnosis

• History: fever, headache, chills, sweats, malaise; focal neurological deficits—acute or subacute; infections in paranasal sinuses, mastoid, or elsewhere; intravenous drug use.

• Signs: Fever, leukocytosis; heart murmur; focal neurological deficits.

• Laboratory studies: MRI imaging; lumbar puncture, if not contraindicated by papilledema or presence of a mass lesion on MRI scanning; blood cultures, where appropriate.

The presence of fever, headache, focal neurological deficits, alterations of mental status, seizures, or some combination of these features suggests both focal disturbance of brain parenchyma and meningeal irritation. The range of conditions that can produce these disorders is large. Among the noninfectious causes, one must consider cerebrovascular disorders and primary or metastatic cancer as leading possibilities. In approaching such problems, it is important to try to determine the precise tempo of progression of the problem (ie, did the symptoms appear and become maximal in seconds to minutes, over a few hours, or over days?). Apoplectic onset or a seizure suggests an embolic process, whereas the development of a deficit over minutes to hours is more consistent with thrombosis or hemorrhage. Slower developing deficits suggest the growth of a mass lesion or sequential vascular insults which become additive.

Bacterial Endocarditis

The neurological complications of bacterial endocarditis are multiple, but the most frequent are those due to multiple emboli with infarction of the brain. Although larger emboli can cause obvious strokelike syndromes (most often in middle cerebral artery distribution), multiple smaller emboli may produce complex confusion states admixed with lesser degrees of focal disturbance. Brain abscesses, although infrequent in endocarditis, are usually associated with S aureus endocarditis and, if present in endocarditis, are usually small. They usually resolve with antimicrobial therapy alone. The formation of mycotic aneurysms at the site of embolism is not uncommon and may occur late in the course of the condition. As noted above, rupture of such aneurysms may be fatal.

One must be alert to the possibility of bacterial endocarditis in any patient with known congenital or acquired alteration of the heart valves, particularly if there has been recent oral or urogenital surgery or intravenous drug use. The traditional signs and symptoms of subacute bacterial endocarditis include asthenia, arthralgias, myalgia, anorexia, heart murmurs, splenomegaly, Roth spots, clubbing, fever, and sweats. Most such cases were caused, in the preantibiotic days, by oral streptococci, which have intrinsically low virulence, infecting heart valves damaged by rheumatic fever and causing small vegetations. However, such cases are now less prevalent and, with increasing intravenous drug use, S aureus, which can infect normal heart valves, is an increasingly prevalent cause of endocarditis. S aureus causes "acute" endocarditis with large vegetations, which embolize to cause metastatic abscesses, Osler's nodes, and, a much more toxic appearance than is typical of subacute endocarditis. The metastatic abscesses in staphylococcal endocarditis often occur in the brain and other parts of the CNS, so that the first presentation of endocarditis is often (20-40%) with stroke or another neurologic problem. The signs of endocarditis may all be easily overlooked, and the cause of the neurologic dysfunction missed if attention is devoted exclusively to the neurological phenomena. Thus, fever in the patient with neurologic findings should prompt a search for signs and symptoms of endocarditis, outlined above. The diagnostic criteria have recently been codified by Durack et al (1994). Once endocarditis is suspected, the most sensitive and specific diagnostic study is the transesophageal echocardiogram (ECHO). Repeated blood cultures may be required to identify the causative organism, but identification of the infecting microorganism and quantitative determination of its susceptibility to antibiotics are of critical importance in determining the nature and duration of treatment with intravenous antibiotics.

Herpes Simplex Virus-Induced Encephalitis

Encephalitides caused by viral infection of the brain frequently result in acutely or subacutely developing syndromes that combine headache, fever, alterations of mental status, seizures, and focal deficits. The most frequent cause of sporadic viral encephalitis is herpes simplex virus (HSV). The process in neonates is most frequently due to HSV type 2 (HSV2) resulting from maternal genital infection that was present at the time of birth. In children or adults, the encephalitic process is almost always caused by type 1 HSV (HSV1). Whether the brain infection results from exogenously acquired virus or from virus resident in cranial sensory ganglia or in the brain has not been determined.

In children or adults, the process usually takes place over a few hours to days. Initially the patient may exhibit behavioral changes or loss of memory or occasionally may complain of unusual olfactory or gustatory sensations. If present, these are valuable hints that herpes encephalitis should be considered. These symptoms may be followed by the development of headache, fever, focal deficits (hemiparesis or aphasia), and progressive disturbance of consciousness. Signs of meningeal irritation (stiff neck or vomiting) are often lacking. The diagnosis is most easily established by an MRI scan combined with typical CSF changes. The MRI scan is more sensitive than a CT scan for detecting HSV1 encephalitis; CT scans often appear normal during the first several days of the illness (when therapy is likely to have the greatest impact). Abnormalities on an MRI scan typically consist of contrast-enhancing lesions (bright on T-2-weighted images) in the medial temporal lobe and inferior frontal lobe, often extending medially and upwards into the putamen. Occasionally a seemingly separate area of disease is present in the cingulate gyrus.

The lesions are often associated with cerebral edema, and they are often bilateral, though rarely symmetrical. In our experience the lesions of HSV may be mimicked by cerebrovascular lesions in the temporal lobe or by the lesions associated with mitochondrial encephalopathies. The CSF is abnormal with a lymphocytic pleocytosis and moderately elevated protein concentration. The presence or absence of erythrocytes in the CSF is not of diagnostic help. Use of the HSV1 PCR to detect the presence of HSV genomes in CSF is generally very sensitive and highly specific, and this method has generally supplanted brain biopsy for diagnosis. The test may be falsely negative on the first day or two of the illness and after the second week. Tests for HSV antibody in the CSF are rarely positive early in the disease; cultures for HSV are almost always negative. The electroencephalogram may point to the presence of a temporal lobe abnormality; however, it is not highly specific for HSV infection. Nonetheless, a normal electroencephalogram weighs against a diagnosis of HSV encephalitis.

Treatment with intravenous acyclovir should be instituted as soon as the diagnosis is suspected, because delay in treatment is associated with a poorer outcome. With early, specific therapy, the mortality and morbidity are substantially reduced, and there is little risk from the drug except in patients with renal failure.

Arbovirus-Induced Encephalitis

A variety of arthropod-borne viruses (togaviruses) cause encephalitis, often in localized outbreaks associated with summertime increases in mosquito populations. The treatment of these encephalitides requires excellent supportive care until the patients improve on their own; there are no currently available specific antiviral compounds that are effective against arboviruses.

Brain Abscesses

A variety of bacterial infections must be considered in producing the brain abscess symptom complex. Brain abscesses commonly cause seizures, focal deficits, and, as they enlarge, progressive obtundation. Although many patients with brain abscesses have no evident primary source of infection, it is imperative to search carefully for a primary focus in the paranasal or mastoid sinuses with contiguous spread to the brain. These sites may yield the organism(s) causing the brain abscess. Additionally, metastatic (or "hematogenous") abscesses, ones seeded via the bloodstream, can arise from infection in skin or lung, by IV drug use, in association with endocarditis, or in association with dental procedures.

Brain abscesses are usually recognized by contrast-enhanced CT or MRI scans. The importance of performing CT or MRI scans with contrast enhancement when testing for brain abscesses is demonstrated in Figure 7-1. Brain abscesses may be confused with brain tumors but are usually more spherical with thinner walls; gas, if present, is a valuable diagnostic feature indicating their bacterial etiology. Brain abscesses are often associated with marked degrees of cerebral edema.

Management of patients who have brain abscesses usually involves a combination of surgery for diagnosis and drainage or excision, antibiotic therapy, and treatment of cerebral edema. The bacterial flora causing brain abscesses are highly variable and are often composed of mixed aerobic and anaerobic bacteria. Staphylococci, anaerobic streptococci, and Bacteroides species predominate, but gram-negative bacilli may also be found in brain abscesses. Initial treatment should include a penicillinase-resistant penicillin such as nafcillin or oxacillin to treat a staphylococcal component, a third-generation cephalosporin for gram-negative organisms, and metronidazole for anaerobic streptococci and Bacteroides species. Some authors include an anti-Pseudomonas drug if the abscess complicates chronic otitis.

Stereotaxic surgical aspiration is advisable to establish bacteriologic diagnosis and is often useful to decompress large abscesses or abscesses that block or threaten to rupture into the ventricular system. Repeated aspirations may be necessary to control a mass effect. Abscesses tend to enlarge by extending toward the ventricular system, and they pose a risk for rupture into the ventricles with an often fatal outcome. Thus, drainage efforts must be especially vigorous with abscesses enlarging toward the ventricular surfaces. Extirpation of abscesses should be considered when they are solitary, well encapsulated, and surgically accessible. Surgical extirpation should be considered for posterior fossa abscesses because of their propensity to compress the brainstem and to obstruct the ventricular system.

Management of the cerebral edema that accompanies brain abscesses should include dexamethasone administered intravenously. Mannitol may be used, especially as a temporizing measure prior to surgical drainage. Note that the cessation of steroid therapy, used to diminish cerebral edema, may allow an increase in the inflammatory component of the abscess, with a resulting increase in the degree of enhancement of the abscess wall on contrast-enhanced CT scans. This phenomenon may unnecessarily raise alarm that the abscess is not yielding to therapy; but this conclusion may be erroneous in the face of steroid withdrawal.

Subdural Empyemas

Abscesses in the subdural space (subdural empyemas) are often associated with frontal, sphenoid, or ethmoid sinus infection. For reasons that are not understood, these empyemas are seen almost exclusively in males. Because the subdural space is continuous over the entire surface of the brain and between the hemispheres, large amounts of pus can be contained within it, causing widespread irritation and edema of the underlying brain. The organisms responsible are similar to those in brain abscesses, with aerobic streptococci, anaerobic streptococci, S aureus, and Bacteroides species predominating. In addition, S pneumoniae and H influenzae may cause these empyemas. Often there is associated meningitis if organisms and/or cells spread through the arachnoid into the subarachnoid space. In addition, involvement of cortical veins and venous sinuses in the inflammatory process and possibly with associated thrombosis can be seen.

Seizures are common. Because the CSF is usually abnormal and under raised pressure in these cases, the hazard of a spinal tap often outweighs the potential value of the information that can be gained. The diagnosis is most readily established by MRI or CT scan with contrast enhancement. The treatment consists of prompt surgical drainage through bilateral or multiple burr holes or by means of formal craniotomy. Provisional antibiotic choices can then be modified on the basis of Gram staining and culture of the aspirated pus.

Cerebral Venous Sinus Infections

Infections of the cerebral venous sinuses can be seen in association with any of the above purulent infections (meningitis, brain abscess, or subdural empyema) or as a consequence of mastoid or sinus infection. Usually the venous sinus involved is contiguous to an infected structure such as an infected sinus. The lateral venous sinuses thus may be involved when there is mastoid or ear infection, and cavernous sinus thrombosis may be associated with ethmoid or sphenoid sinus infection or with facial cellulitis. With extension of infective thrombus into cortical veins, seizures and cortical venous infarction are common. Infections of the cavernous sinus may produce proptosis and chemosis of the eye and palsies of the third, fourth, and sixth cranial nerves because these nerves traverse the cavernous sinus. This constellation of signs is also seen in diabetics with nasal or sinus infection caused by Mucor or Rhizopus fungal species. Involvement of the superior sagittal sinus frequently produces cortical vein thrombosis with seizures and may result in infection of the upper convexities of the brain with consequent leg paralysis.

The diagnosis of thrombosis of these venous structures is best made by MRI scanning, which can demonstrate the presence or absence of flow voids, clotted blood, engorgement of these structures, or some combination of these findings. The diagnostic certainty can be further enhanced by the use of magnetic resonance venography.

Treatment consists of antibiotics as for the treatment of brain abscesses or for other specific causative microorganisms that may be identified. Consideration should be given to administration of anticoagulants to inhibit the propagation of clots within the venous sinuses. However, the use of anticoagulants must be weighed against the possibility of worsening the process by hemorrhage, accompanying venous occlusion and infarction of brain.

Fungal Infections

Fungi may cause focal disease in the brain with a constellation of signs and symptoms similar to those considered above. Fungal infections are most often encountered in hosts with compromised cell-mediated and other types of immunity. They are thus seen more often in patients with AIDS, lymphoma, Hodgkin's disease, leukemia, or advanced diabetes or in patients receiving cytotoxic or immunosuppressive regimens. Cryptococcal infection usually presents as severe meningitis and should be considered in the differential of acute bacterial meningitides discussed earlier. Infection caused by Mucor or Rhizopus species occurs most frequently in diabetics with multiple episodes of acidosis. The infection may spread from the oropharynx or paranasal sinuses into the skull base, involving the orbit, cranial nerves two through six, and the cavernous sinus as well as the carotid artery. The clinical picture of a red or proptotic eye with third or sixth nerve paralysis in a diabetic should prompt aggressive biopsy and culture of affected tissues as well as culturing of the nasopharynx and sinuses for Mucor or Rhizopus species. Optimal management requires a combination of surgical debridement and therapy with high-dose amphotericin B or lipid-formulated amphotericin B.

The most frequent fungi associated with parenchymal infection of brain are Aspergillus and Candida species. These infections are seen most frequently in immunocompromised hosts, particularly in those with neutropenia. Aspergillus infections usually have their origins in pulmonary or sinus infections whereas Candida infections are often seen in patients with indwelling intravenous lines, in intravenous drug users, or in patients who have previously been treated with corticosteroids or broad-spectrum antibiotics.

These organisms, especially Aspergillus and Mucor or Rhizopus species, share a predilection for invading the walls of cerebral blood vessels with resulting thrombosis of the blood vessel. Thus, in addition to causing cerebral abscesses and meningitis, they often produce strokelike events as a result of thrombi forming in inflamed vessels. Treatment of these fungal infections is with high-dose amphotericin B or lipid-formulated amphotericin B. Therapy for Candida infection is amphotericin B or lipid-formulated amphotericin B with or without 5-fluorocytosine, depending on the patient's underlying disease and the species of the Candida strain (some strains of certain species of Candida, such as parapsilosis, are exquisitely susceptible to the synergism of amphotericin B with 5-fluorocytosine).

Toxoplasmosis

Toxoplasmosis in the CNS presents most commonly with multifocal lesions, causing focal deficits, seizures, and impairment of cognitive functions over a period of days to weeks. Before the advent of AIDS, CNS toxoplasmosis was encountered only rarely, and then usually in the setting of Hodgkin's disease, lymphoma, or other states of severe immunosuppression. It has become a frequent complication in AIDS patients and should be immediately considered in the AIDS patient who develops multifocal neurologic deficits over a period of a few days to weeks.

The disease is often easily visualized by contrast-enhanced CT or (preferably) MRI scans, most often appearing as multicentric solid or ringlike enhancing lesions in the brain; the appearances are often quite characteristic but can be mimicked by cerebral lymphoma, also an AIDS-associated condition. A negative immunoglobulin G antibody test for Toxoplasma gondii makes the diagnosis unlikely. If the immunoglobulin G antibody test is positive, some experts advocate a therapeutic trial of sulfadiazine pyrimethamine, and folinic acid, in association with monitoring the clinical course as well as the size of the cerebral lesions on MRI scan. If there is no response in 10-14 days or if there is deterioration, a brain biopsy to examine other diagnostic possibilities should be strongly considered.

Read more...