The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Joel Ruff. This current second edition chapter is a revision and update of the original author’s work.
A 15-year-old boy comes to the office for a sore throat. His sore throat began three days ago, but was mild, and thus he did not seek medical attention. He denies any initial fever, vomiting, diarrhea, rash, rhinorrhea or cough. Last night, his sore throat became worse, seeming to be more painful on the right. This morning the pain persisted on the right and made it difficult to swallow or open his mouth. He has been well otherwise and cannot remember when he last had a sore throat. His energy level is normal and he denies other symptoms except for the severe pain.
Exam: VS T 39.0, P 100, R 20, BP 130/84. In general, he looks uncomfortable although not toxic. He has difficulty opening his mouth wider than 2 cm. His speech has a "hot potato" (muffled) quality to it. His mucous membranes are moist. An asymmetric erythematous swelling (greater on the right) and deviation of the uvula to the left are seen. The right side of his soft palate is also noted to be slightly bulging. His neck is supple with tender adenopathy on the right side. The remainder of his general physical examination is normal including lungs, heart, abdomen, extremities and skin.
He is referred to the emergency room. A diagnosis of peritonsillar abscess is made and he undergoes incision and drainage, spending a few days in the hospital for IV antibiotics and pain control. He is discharged in good condition a few days later.
Upper respiratory infections include infectious conditions of the nose, adenoids, tonsils, pharynx, oral cavity and larynx. The following terms are often used: Rhinitis (nose), tonsillitis (tonsils), pharyngitis (pharynx), nasopharyngitis (nose and pharynx), stomatitis (mouth), gingivitis (gums), gingivostomatitis (gums and mouth), uvulitis (uvula), glossitis (tongue), laryngitis (larynx), parotitis (parotid gland). Sinusitis and otitis media are discussed in separate chapters.
Pharyngitis is a ubiquitous condition that accounts for a large number of visits to the physician. Fortunately, the majority of causes of sore throat have a benign course requiring only symptomatic treatment. It is important, however, to have an understanding of some of the less common, but potentially more serious etiologies of pharyngitis and their sequelae.
The tonsils are the site of most of the infections discussed below. They, along with the adenoids superiorly and lingual tonsils inferiorly, form a ring of lymphatic tissue known as the Waldeyer ring. What is referred to most commonly as "tonsils," are the palatine tonsils, which form the lateral limits of the ring. The tonsils are bounded by the palatoglossus muscle (anterior pillar) and palatopharyngeal muscle (posterior pillar). The structures have multiple folds, which increase surface area available for antigenic stimulation. When an antigen is presented, it stimulates B cells that have congregated there. Migration of more lymphocytes to the site occurs and they then differentiate into immunoglobulin producing cells. Although IgM and IgG are found, the majority of the secretion consists of IgA. A wide variety of organisms can cause infection in this area, including viruses, bacteria, fungi and parasites (1,2).
Viruses cause the majority of pharyngitis, rhinovirus being the most common, followed by coronavirus and adenovirus (3). Upper respiratory infection etiologies are frequently age-dependent. For example, respiratory syncytial virus (RSV) will cause cold symptoms in teens and adults, while it causes bronchiolitis in infants and pneumonia in small and/or premature infants. Parainfluenza virus causes colds in teens and adults, while it causes croup in young children.
A long list of other viruses may also cause infection including influenza, herpes simplex virus (HSV), coxsackie virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV). While the majority of viral infections have nonspecific symptoms, a few virus types give clues to their identity in how they present.
Adenovirus, for example may cause an associated conjunctivitis, the combination of which is known as "pharyngoconjunctival fever" (3,4). Herpes and coxsackie virus may produce ulcerations on the oral mucosa (stomatitis). HSV type 1 tends to be the more common subtype of HSV, but oral-genital exposure to HSV type 2 may also produce similar lesions. The lesions from HSV tend to, but not exclusively, be more anterior in the mouth and often involve the gums (known as gingivostomatitis) (3). Lesions from coxsackie virus, which is a subtype of enterovirus, may appear similarly as multiple vesicles on an erythematous base (commonly seen on the palate), and are known as herpangina. The lesions in the latter may be associated with vesicles on the hands and feet and in this case are known as "hand-foot-and-mouth disease." Both types of oral ulcerations are very painful.
Infectious mononucleosis, the prototypical disease of Epstein-Barr virus, manifests as a triad of fatigue, pharyngitis, and lymphadenopathy. In industrialized countries, the majority of patients are adolescents and young adults. However in developing countries, most EBV transmission occurs during infancy and early childhood, resulting in asymptomatic or mild disease (14). Differentiation from group A streptococcal pharyngitis may be difficult since both may have thick, exudative tonsillitis and palatal petechiae. Systemic symptoms may be the clue to diagnosis, with lethargy and malaise commonly prominent, in addition to hepatosplenomegaly, which is not associated with streptococcal pharyngitis. Not only are anterior and posterior chain lymph nodes in the neck enlarged, but axillary and inguinal adenopathy often occurs. Splenomegaly (50% of cases) and hepatomegaly (10-15% of cases) can be seen, but frank jaundice is seen in only about 5%. A rash is classically elicited in up to 80% of patients treated with ampicillin (and amoxicillin), but may be seen in 5% of patients who do not receive antibiotics. The complete blood count may show thrombocytopenia (sometimes marked but usually mild). Lymphocytosis, often with more than 10% atypical lymphocytes, can been seen on the differential (3). Testing for EBV can be done with a "Monospot" test that detects heterophile antibodies in the patient's serum which agglutinate sheep or horse erythrocytes. The sensitivity is about 90%, but it is often much less in infants and children less than 4 years old. Although several drugs have activity against EBV, none are effective for routine use. The mainstay of treatment is symptomatic management. Advice to avoid vigorous activities for one month after onset of illness will help protect against splenic rupture (3). Antiviral medications (acyclovir) have been shown to decrease viral replication and oropharyngeal shedding, but do not reduce the severity or duration of illness (14). Corticosteroids should only be used to prevent occlusion of the airway by enlarged tonsils or in other special cases such as massive splenomegaly, myocarditis, hemolytic anemia and hemophagocytic syndrome (4).
A final virus that deserves to be included in the differential is HIV. After a period of incubation ranging from 6 days to 5 weeks, fever, nonexudative pharyngitis, lymphadenopathy, lethargy, myalgia and arthralgia develop in acute HIV infection. The higher incidence of rash in acute retroviral syndrome (40-80% versus 5%) and the occurrence of mucocutaneous ulceration may help differentiate the above from infectious mononucleosis, which can have similar constitutional symptoms and sore throat. Diagnosis is further complicated by the fact that tests for HIV antibody are often negative during this time, so assays for p24 antigen or HIV RNA must be used if the diagnosis is suspected. The diagnosis is important to make because during this period, the patient benefits from maximal therapy with antiretroviral agents (3).
Group A streptococcal (GAS) pharyngitis is the most common bacterial cause of sore throat, comprising 15-30% of sore throats in children and a smaller percentage in adults (5-10%). GAS pharyngitis is treated to shorten the course slightly, to reduce transmission to others, and to avoid suppurative sequelae (peritonsillar or retropharyngeal abscess, cervical lymphadenitis, mastoiditis, otitis media and sinusitis) and non-suppurative sequelae (acute rheumatic fever). Although there is no evidence that treatment of GAS pharyngitis prevents the development of post-streptococcal glomerulonephritis, a course of systemic antibiotics, usually penicillin, is recommended in patients with the latter condition when the diagnosis is made. This is to prevent the spread of nephritogenic strains, but it has not been shown to alter the course of the glomerulonephritis (3). Both post-streptococcal glomerulonephritis and acute rheumatic fever can result from pharyngeal GAS infection, but with skin infection (impetigo) the only non-suppurative sequelae is post-streptococcal glomerulonephritis.
Rheumatic fever deserves special mention because of its historical significance in the U.S. It continues to be a significant cause of morbidity and mortality in many populations of the world, including in Hawaii. Around the year 1900, rheumatic fever and its sequelae were the leading causes of death among school-age children. Although known to be associated with sore throat, the lack of identification of streptococci in damaged heart valves and elsewhere puzzled investigators until about 1930 when the association between antibodies and their effect on various tissues involved in the illness began to be elucidated. First with sulfa and subsequently with penicillin, streptococcal pharyngitis has been treated successfully since World War II. The decline in the incidence of acute rheumatic fever over the past 100 years, however, began before the advent of antibiotic availability and has been attributed to a decrease in the rheumatogenicity of streptococci (5). Astute observations in the 1980s of similarities in areas of the brain affected in Sydenham's chorea and obsessive-compulsive disorder (OCD) and exacerbation of OCD with GAS infection led to interest in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections ("PANDAS") (7). Currently, evidence does show a post-streptococcal autoimmune etiology for OCD in some patients. However, there is controversy among experts as to whether PANDAS as a syndrome is valid. Additionally, there is no evidence that supports the use of prophylactic antibiotics and immunnomodulatory therapy (intravenous immune globulin G and plasma exchange) to prevent exacerbations in patients with PANDAS (16). Research continues in this field related to this disease.
Discussion on how to diagnose GAS pharyngitis clinically has not been definitively settled. Certain factors such as the typical age group of school age children, exudative appearance of tonsils, anterior cervical adenopathy, appropriate season (mid-winter to early spring) and absence of rhinorrhea and cough make the diagnosis of GAS pharyngitis likely (60-70% in children and 20-30% in adolescents) (3,6). Recommendations for whom to test vary and are defined in detail in the Red Book (4). Examples of factors to consider include viral symptoms such as coryza (acute inflammation of nasal mucosa with discharge, i.e., a cold), conjunctivitis, stomatitis, hoarseness, or diarrhea which make GAS pharyngitis less likely, or prior history in the patient or a family member of nonsuppurative sequelae which should cause stronger consideration for testing. GAS pharyngitis in children below 3 years old is very uncommon (4). A properly done throat culture, which includes vigorous swabbing of both tonsils and the posterior pharynx remains the best diagnostic test available with about a 90-95% sensitivity (3,4,15). The rapid antigen detection test (RADT) can be used for likely GAS pharyngitis patients whose throat cultures will not be available for more than 48 hours (17). RADT measures group A streptococcal carbohydrate antigen in a few minutes, as opposed to the 24-48 hours for a throat culture. RADT has gained popularity but have sensitivities that are 80-90% at best. It is recommended that a negative rapid streptococcal test be followed up with a throat culture in suspicious cases (15). Neither test will differentiate a carrier from a patient with an acute infection (3).
Since most throat infections have a viral etiology, it is difficult to explain why one study showed that 70% of children and adolescents seen for sore throats in primary care settings received antibiotics (8). A study in military recruits in the 1950s showed that there is a window of 9 days from onset of pharyngitis during which administration of antibiotics is effective to prevent acute rheumatic fever. Since acute GAS pharyngitis lasts only 2 to 5 days without treatment, this means that rheumatic fever can still be prevented after the symptoms of pharyngitis are gone (6). Penicillin remains the drug of choice and should be continued for a full ten days or given intramuscularly in the procaine/benzathine formulation. Amoxicillin once daily has been shown to be as effective as three times daily penicillin and is also considered more palatable, resulting in better compliance (9,20).
Different types of streptococci including serogroups C and G may also cause pharyngitis via food and waterborne routes of infection. Although these types may cause glomerulonephritis, they are not associated with acute rheumatic fever. The infections tend to be milder than those with group A streptococci. Treatment, however, is recommended when these organisms are identified in symptomatic patients although the proven benefits are unknown. The same antibiotics that are used for group A streptococci are effective for types C and G (3).
Arcanobacterium haemolyticum is a rare cause of pharyngitis that usually occurs in adolescents or young adults. The illness may mimic group A streptococcal infection including a scarlatiniform rash. Erythromycin is the drug of choice, but the clinical benefit is uncertain (3,18). Neisseria gonorrhoeae may cause a pharyngitis if inoculated into the pharynx by oral contact with infectious material. Usually, the infection is asymptomatic but clinical pharyngitis and tonsillitis may develop. Disseminated disease should be suspected if Neisseria gonorrhoeae is found. Special media is required if the diagnosis is suspected. The treatment is ceftriaxone 125mg IM. Fluoroquinolones are no longer recommended for gonorrhoeae infections due to widespread resistance in the US (19). Treatment should also target against co-infection with C. Trachomatis with a single dose of azithromycin 1 g by mouth or with doxycycline 100 mg twice a day, by mouth for 7 days, if chlamydial infection has not been ruled out (19).
Diphtheria is now a rare disease in the US, but currently has ongoing morbidity and mortality in other areas of the world such the central Asian republics, Russia, and Ukraine (3,4). The characteristic finding is the grayish brown diphtheric pseudomembrane which may involve the tonsils unilaterally or bilaterally and can extend to involve the soft palate, nares, pharynx, larynx or even the tracheobronchial tree (3). Case fatality rates range from 3% to 23%, the usual mechanisms of morbidity and mortality being upper airway obstruction from extensive membrane formation or soft tissue edema and myocarditis. Peripheral neuropathy may also occur (4). Edema of the soft tissues in the neck and prominent cervical and submental adenopathy may give the patient a "bull-neck" appearance (3). The disease is best prevented by immunization, but if necessary, is treated with equine antitoxin and antibiotics, erythromycin or penicillin G intravenously. Antimicrobial therapy alone is not a substitute for antitoxin (4).
Mycoplasma pneumoniae may cause pharyngitis, but since it is also commonly isolated from controls, the significance of such infections remains unknown. Chlamydia pneumoniae has also been reported to cause pharyngitis either by itself or preceding pneumonia. Since routine testing does not diagnose either of these organisms, treatment is not likely to be offered. The incidence of these organisms is likely seen in only a small percentage of infections and since serious complications are not commonly observed, it is likely that these infections resolve without treatment in most instances. (3,6)
Peritonsillar abscess is one of the listed suppurative sequelae of group A streptococcal infection but may also occur as a result of infection from other oral anaerobes. It is more common in adults than in children (15). Chronic tonsillitis is a predisposing factor. Acute tonsillopharyngitis precedes the formation of abscess, usually with an afebrile period noted or unresolving fever before the onset of severe throat pain. There may be trismus (pain on opening the mouth) and refusal to speak or swallow because the pain may be so intense. On exam, one of the tonsils is usually markedly swollen, with effacement of the anterior tonsillar pillar and deviation of the uvula to the opposite side. Untreated abscesses may rupture into the airway. Treatment involves incision and drainage of the abscess and intravenous antibiotics. Penicillin may be used although some prefer clindamycin for better anaerobic coverage. Without a history of chronic tonsillitis, there is a 10% recurrence rate. Authorities vary on whether tonsillectomy should be performed after the initial episode (2,10). Acutely, there is no evidence of benefit of tonsillectomy (15).
Retropharyngeal abscess can also manifest as a complication of bacterial pharyngitis or less commonly from extension of vertebral osteomyelitis or penetrating injury to the posterior pharynx. The potential space between the posterior pharyngeal wall and the prevertebral fascia contains lymphatic tissue that involutes around age 3 to 4 years, making infection less common after that age. A child with a preceding acute nasopharyngitis or pharyngitis who refuses to eat, has high fever, severe distress, hyperextension of the neck or noisy gurgling respirations may have a retropharyngeal abscess. Imaging (lateral neck radiographs) is essential to confirm the diagnosis, although in an uncooperative child, a bulge in the posterior pharynx may be seen. To obtain a proper soft tissue lateral neck x-ray, the neck should be in full extension (lordotic) and the x-ray should be taken in end-inspiration. False positive x-rays (false widening of the prevertebral soft tissue) may occur with poor positioning. Untreated retropharyngeal abscesses may rupture into the airway or spread down the fascial planes to the mediastinum. Treatment starts with empiric antibiotic therapy, which is effective in 25% of cases. Close airway monitoring and surgical consultation is important as well. Refractory cases are treated with surgical management, which includes incision and drainage under general anesthesia and empiric intravenous antibiotics with coverage for Staphylococcus aureus until culture and sensitivity information is available (2,10). CT-guided needle aspiration is an alternative that causes less trauma and avoids general anesthesia (15). A "cold" abscess with tuberculosis may present as a retropharyngeal abscess (11).
Candida may cause infection of the pharynx under conditions of altered immunity such as HIV infection, immunodeficiency or diabetes (11). Thrush (mild oral candidiasis) is common in healthy infants. White plaques may be seen on the buccal mucosa and the tongue. Initial treatment is with oral nystatin.
Mechanical problems such as tonsillar hypertrophy leading to obstructive sleep apnea and chronic mouth breathing may cause pharyngitis. Foreign body must always be included in the differential of sore throat that does not appear infectious. Asymmetric swelling of the tonsils without infection may be a clue to malignancy (2,11). Adult type epiglottitis should be considered in older children and teens complaining of a severe throat without much clinical findings. Diagnoses such as chronic fatigue syndrome contain sore throat as part of their criteria but continue to be controversial. Emerging entities include PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis, and adenitis-cervical) (12). It is the most common cause of periodic fevers in children and is considered an autoinflammatory disease. However a genetic marker has not yet been identified and thus pathogenesis remains unknown (21).
Pharyngitis can have a myriad of causes, but for the most part, the causes are easily managed viral infections. The physician must have a certain awareness of the more serious problems which can present as pharyngitis and the appropriate workup and management once the diagnosis is suspected. Certain clues can help the physician diagnose the more serious causes of sore throat and treat them appropriately.
1. A 12 year old male with 4 days of sore throat comes into the office. He has been afebrile, has rhinorrhea, cough and one day of diarrhea associated with his sore throat. The throat is mildly erythematous with otherwise normal appearing tonsils. The best course of action is (this may be a controversial question depending on your practice setting):
. . . . . a. Swab his throat and give a 10 day course of antibiotics. You will call him if the culture is negative for group A strep so that he can stop antibiotic treatment.
. . . . . b. Swab his throat and withhold antibiotics unless his culture is positive.
. . . . . c. Advise him on symptomatic treatment.
. . . . . d. Give him antibiotics without testing for group A strep.
2. A 14 year old boy who you know is homeless and possibly engaging in prostitution comes into clinic complaining of sore throat, rash and pronounced fatigue. One exam, he has an exudative pharyngitis. Tests to consider include (choose all that apply):
. . . . . a. Throat swab for group A strep.
. . . . . b. HIV test for antibody.
. . . . . c. Throat swab for Neisseria gonorrhoeae.
. . . . . d. Monospot for EBV infection.
3. A 3 year old is very fussy, febrile and has profuse rhinorrhea. On exam, shallow ulcers are noted on the soft palate and vesicles are noted on one palm and both soles of the feet. The etiology of this infection is likely:
. . . . . a. Group A streptococci
. . . . . b. Arcanobacterium haemolyticum
. . . . . c. Coronavirus
. . . . . d. Coxsackievirus
4. A 6 year old child recently adopted from somewhere in Russia complains of sore throat and is noted by the parents to have a lot of "grayish junk" in his mouth and nose. Exam shows an adherent grayish-white membrane over both tonsils and the soft palate that, when removed, leave an edematous, bleeding area of tissue. After calling your state health department, you initiate therapy with:
. . . . . a. Intravenous erythromycin or penicillin G.
. . . . . b. The above antibiotics plus antitoxin.
. . . . . c. Antitoxin alone.
. . . . . d. IVIG.
5. In children, nonsuppurative sequelae of group A strep infection of the pharynx include (circle all that apply):
. . . . . a. Post streptococcal glomerulonephritis.
. . . . . b. Acute rheumatic fever.
. . . . . c. Periodic fever syndrome.
. . . . . d. PANDAS (maybe).
Case of retropharyngeal abscess compared to croup and epiglottitis: Boychuk RB. Drooling, Stridor, and a Barking Cough: Croup?? In: Yamamoto LG, Ina AS, DiMauro R. Radiology Cases In Pediatric Emergency Medicine, 1994, volume 1, case 10. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v1c10.html
Series of lateral neck radiographs, some of which are retropharyngeal abscesses: Yamamoto LG. Test Your Skill In Reading Pediatric Lateral Necks. Yamamoto LG, Inaba AS, DiMauro R. Radiology Cases In Pediatric Emergency Medicine, 1995, volume 2, case 20. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v2c20.html
Retropharyngeal abscess case: Inaba AS. Fever with Neck Stiffness...Rule-Out Meningitis? In: Yamamoto LG, Inaba AS, DiMauro R. Radiology Cases In Pediatric Emergency Medicine, 1996, volume 5, case 1. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v5c01.html
1. Gross CW, Harrison SE. Tonsils and adenoids. Pediatr Rev 2000;21(3):75-78.
2. Richardson MA. Sore throat, tonsillitis and adenoiditis. Med Clinic of North Am 1999;83(1):75-83.
3. Bisno AL. Acute pharyngitis. New Engl J Med 2001;344(3):205-211.
4. Section 3-Summaries of Infectious Diseases-Diptheria, Enterovirus (Nonpolio) Infections, Epstein-Barr Virus Infections (Infectious Mononucleosis), Group A Streptococcal Infections. In: Diseases, American Academy of Pediatrics. 2000 Red Book, 25th edition. 2000, Elk Grove Village: American Academy of Pediatrics, pp. 230-234, 236-238, 238-240, 526-536.
5. Mirkinson L. The Diagnosis of rheumatic fever. Pediatr Rev 1998;19(9):310-311.
6. Pichichero ME. Group A Beta-hemolytic Streptococcal Infections. Pediatr Rev 1998;19(9):291-302.
7. Swedo SE. Genetics of Childhood Disorders: XXXIII. Autoimmunity, Part 6: Poststreptococcal Autoimmunity. J Am Acad of Child Adolesc Psychiatry 2001;40(12):1479-1482.
8. Nyquist AC, Gonzales R, Steiner JF, et al. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA 1998;279(11):875-877.
9. Felder HM, Gerber MA, Randolph MF, et al. Once-daily therapy for Streptococcal pharyngitis with amoxicillin. Pediatrics 1999;103(1):47-51.
10. Arnold JE. Chapter 327-Infections of the upper respiratory tract. In: Behrman RE, Kliegman RM, Arvin AM (eds). Nelson Textbook of Pediatrics, fifteenth edition. 1996, Philadelphia: WB Saunders Company, pp. 1187-1193.
11. Drake-Lee A. Clinical Otolaryngology, first edition. 1996, Singapore: Longman Singapore Publishers, pp. 159-184.
12. Thomas KT, Feder HM, Lawton AR, et al. Periodic fever syndrome in children. J Pediatr 1999;135(1);15-21.
13. Long SS. Syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) - What it isn't. What is it? J Pediatr 1999;135(1):1-5.
14. Jenson HB. Epstein-Barr Virus. Pediatrics in Review 2011;32;375-384
15. Gereige R, Sautu BC. Throat Infections. Pediatrics in Review 2011;32;459-469
16. Sarvet B. Childhood Obsessive-Compulsive Disorder. Pediatrics in Review 2013;34;19-28
17. Langlois DM, Andreae M. Group A Stretococcal Infections. Pediatrics in Review 2011;32;423-430
18. Arnold JE. Chapter 373- Acute Pharyngitis. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE (eds). Nelson Textbook of Pediatrics, Nineteenth edition. 2011, Philadelphia: Elsevier Saunders, pp. 1157-1177
19. Center for Disease control and Prevention. Update to CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2006. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5614a3.htm. Accessed February 2013.
20. Baltimore RS. Re-evaluation of antibiotic treatment of streptococcal pharyngitis. Current Opinion in Pediatrics 2010, 22:77–82
21. Vigo G, Zulian F. Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA). Autoimmunity Reviews 2012;12;52–55
Answers to questions
1. Any of these answers may be correct depending on your practice setting.
. . . . . a. for difficult to reach families or someone you don't trust to follow up.
. . . . . b. is probably what you would do for most families you felt comfortable with follow up (i.e., you could reach them on the phone if you needed to).
. . . . . c. is what you might do if you are playing the odds; it's probably viral.
. . . . . d. is what you might do during an epidemic.
2. a, c and d (b - HIV antibody test - is usually negative during this period and PCR for p24 antigen, RNA or reverse transcriptase is required).
4. b (antitoxin must be given with antibiotics)
5. a, b, and d (no one is sure what causes PFAPA)