Evaluation of acute pharyngitis in adults

INTRODUCTION — Acute pharyngitis is one of the most common conditions encountered in outpatient clinical practice. Most cases of acute pharyngitis are caused by respiratory viruses and are self-limited. However, symptoms of viral pharyngitis broadly overlap with pharyngitis caused by important treatable causes, such as group A Streptococcus (GAS) (figure 1). Using a systematic approach to diagnosis can help reduce inappropriate antibiotic use by identifying which patients require testing and treatment for GAS and can also help determine which patients have serious conditions, such as acute human immunodeficiency virus (HIV) infection, highly contagious infection such as coronavirus disease 2019 (COVID-19), or life-threatening complications of infection, such as airway obstruction.

The epidemiology, clinical features, and evaluation of acute pharyngitis in adults are reviewed here. The treatment of streptococcal pharyngitis and the symptomatic management of pharyngitis are discussed separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children" and "Symptomatic treatment of acute pharyngitis in adults".)

EPIDEMIOLOGY — Acute pharyngitis accounts for approximately 12 million ambulatory care visits, or 1 to 2 percent of all ambulatory care visits, in the United States annually [1]. The incidence peaks in childhood and adolescence with approximately 50 percent of all cases occurring before age 18 [2,3]. Among adults, most cases of acute pharyngitis occur by age 40 and incidence declines thereafter [2].

ETIOLOGY AND CLINICAL FEATURES — Causes of sore throat can be broadly categorized as infectious (usually viral or bacterial) and noninfectious. The two most common infectious causes are respiratory viruses and group A Streptococcus (GAS) (table 1).

Most patients with pharyngitis of any cause present with a sore throat that worsens when swallowing. Neck pain or swelling due to regional lymphadenopathy commonly accompany sore throat. Fever, headache, fatigue, and malaise are variably present. The specific microbiologic cause of pharyngitis can rarely be distinguished based on clinical features alone. However, understanding the relative prevalence of the causes of pharyngitis and their clinical features can help focus evaluation.

Infectious causes

Respiratory viruses, including SARS-CoV-2 — Respiratory viruses are the most common causes of acute pharyngitis, accounting for approximately 25 to 45 percent of cases [4-6]. Adenovirus, rhinovirus, and coronaviruses (including severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], the virus that causes COVID-19) are among the leading causes of viral pharyngitis. Other respiratory viruses that cause pharyngitis include enteroviruses, influenza A and B, parainfluenza viruses, and respiratory syncytial virus.

Patients with pharyngitis caused by respiratory viruses usually have other signs and symptoms of upper respiratory tract infection, such as fatigue, nasal congestion, and cough (figure 1). Coryza, conjunctivitis, sneezing, hoarseness, ear pain, sinus discomfort, oral ulcers, and a viral exanthem (picture 1) are additional features that support the diagnosis of viral pharyngitis. Fever associated with viral upper respiratory tract infection is typically low grade except in patients with influenza and COVID-19. Cervical lymphadenopathy may be present but is generally not prominent. (See "The common cold in adults: Diagnosis and clinical features", section on 'Clinical features'.)

Pharyngitis caused by SARS-CoV-2 can occur with or without other signs or symptoms of COVID-19, which is discussed in detail separately. (See "COVID-19: Clinical features".)

Group A Streptococcus — GAS is the most common bacterial cause of acute pharyngitis and is estimated to cause approximately 5 to 15 percent of cases of acute pharyngitis in adults in developed countries [7-12]. Rates are higher in less developed countries [13].

Classic signs and symptoms of GAS pharyngitis include acute-onset sore throat, fever, pharyngeal edema, patchy tonsillar exudates, and prominent, tender, anterior cervical lymphadenopathy (picture 2 and figure 1). Other features that support the diagnosis include palatal petechiae, a scarlatiniform rash (picture 3), and a strawberry tongue (picture 4) (eg, Scarlet fever). Occurrence in a younger adult and exposure to others with GAS pharyngitis also make the diagnosis more likely. (See "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)

In addition to causing acute pharyngitis, GAS infection can lead to suppurative and nonsuppurative complications. Suppurative complications of GAS pharyngitis are due to invasion of the organism beyond the pharynx and include otitis media, peritonsillar cellulitis or abscess, sinusitis, meningitis, bacteremia, and necrotizing fasciitis. Nonsuppurative complications of GAS pharyngitis are immune mediated and include acute rheumatic fever, poststreptococcal glomerulonephritis, and reactive arthritis. Prevention of these complications is a key reason for treating GAS pharyngitis with antibiotics. (See "Treatment and prevention of streptococcal pharyngitis in adults and children" and "Complications of streptococcal tonsillopharyngitis".)

GAS can also asymptomatically colonize the oropharynx, termed chronic carriage (table 2). In general, there is no need to test for or treat chronic carriage. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Definitions' and "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Chronic GAS carriers'.)

Other bacteria

●Group C and G Streptococcus – Group C and G streptococci are generally considered to be less common causes of pharyngitis than GAS [9,14], although cohort studies suggest that these bacteria may account for about 5 to 10 percent of cases of pharyngitis [8,9,15]. Pharyngitis caused by group C or G Streptococcus is clinically indistinguishable from GAS pharyngitis. Infection with group C or G streptococci most often occurs among college students and young adults and has been associated with community and foodborne outbreaks [8,9,15,16]. In contrast with GAS pharyngitis, infection with group C or G streptococci has not been associated with acute rheumatic fever or other immune-mediated complications. (See "Group C and group G streptococcal infection", section on 'Pharyngitis'.)

●Arcanobacterium haemolyticum – A. haemolyticum (formerly Corynebacterium haemolyticum), a facultative anaerobic gram-positive bacillus is an uncommon cause of acute pharyngitis, accounting for about 1 to 2.5 percent of cases [12,17]. Pharyngitis caused by A. haemolyticum is similar to streptococcal pharyngitis and is most common in adolescents and young adults [9,17,18]. A scarlatiniform rash, similar to that seen with Scarlet fever, is common, affecting about 50 percent of patients [17,18]. Severe, invasive infections with A. haemolyticum are rare but have been reported [19-24]. A. haemolyticum is usually resistant to trimethoprim-sulfamethoxazole and may be penicillin tolerant [25]. Treatment of choice in the outpatient setting is erythromycin [26].

●Fusobacterium necrophorum – F. necrophorum, an anaerobe that often colonizes the oropharynx, is a putative cause of pharyngitis. F. necrophorum has been detected in oropharynx of approximately 2 to 10 percent of asymptomatic young adults. Rates of detection are higher in symptomatic patients, ranging from 15 to 21 percent of adults with acute pharyngitis [27-30] and up to 45 percent in adults with recurrent pharyngitis [31,32]. However, copathogens are often detected with F. necrophorum [33], and no study has demonstrated that treatment directed at F. necrophorum leads to resolution of symptoms or prevention of complications [34]. Thus, it is possible that the organism's ecologic niche broadens with pharyngeal inflammation and that F. necrophorum is a secondary invader rather than a causative pathogen. By contrast, F. necrophorum plays a causal role in Lemierre syndrome (septic thrombophlebitis of the internal jugular vein). (See "Lemierre syndrome: Septic thrombophlebitis of the internal jugular vein".)

●Mycoplasma and Chlamydia species – Both Mycoplasma pneumoniae and Chlamydia pneumoniae have been reported to cause pharyngitis, most commonly in children and young adults [35-37]. The precise prevalence is not known, but M. pneumoniae appears to be more common than C. pneumoniae. Pharyngitis caused by either organism is often accompanied by lower respiratory tract infection. (See "Mycoplasma pneumoniae infection in adults" and "Pneumonia caused by Chlamydia pneumoniae in adults".)

●Corynebacterium diphtheriae – C. diphtheriae is the causative agent of diphtheria. While rare in the United States, the prevalence of diphtheria is higher in less developed regions of the world where vaccination rates are low and outbreaks continue to occur [38,39]. The clinical syndrome of diphtheria is characterized by pharyngitis, low-grade fever, malaise, and cervical lymphadenopathy. Symptom onset is usually gradual. The hallmark of diphtheria, the formation of a tightly adherent gray membrane that bleeds when dislodged, occurs in at least one-third of patients (picture 5 and picture 6). Although diphtheria is rare, suspicion should be raised in patients who have recently lived in or traveled to areas where diphtheria remains endemic and in unvaccinated patients. (See "Clinical manifestations, diagnosis, and treatment of diphtheria" and "Epidemiology and pathophysiology of diphtheria".)

●Francisella tularensis – F. tularensis can cause pharyngeal tularemia, particularly when infection is acquired by ingestion of contaminated food or water. Pharyngeal tularemia is characterized by fever and severe exudative pharyngitis, which is often accompanied by oral ulcers and painful cervical lymphadenopathy. As with diphtheria, a pharyngeal membrane may be present. While rare in the United States, tularemia comprises a larger percentage of cases worldwide, particularly in outbreaks that have occurred as a consequence of the disruptions caused by war or natural disaster [40-45]. (See "Tularemia: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Pharyngeal (oropharyngeal) disease'.)

HIV and other sexually transmitted infections — Sexually transmitted infections (STIs) are uncommon causes of pharyngitis, but their prevalence rises considerably among those with high-risk behaviors (table 3) [46-48].

●Acute HIV infection – Acute HIV infection is estimated to be symptomatic (termed acute retroviral syndrome) in approximately 40 to 90 percent of patients [49-51]. Among symptomatic patients, approximately 40 percent have pharyngitis [50]. The presence of painful mucocutaneous lesions is one of the most distinctive characteristics of acute HIV infection. Ulcers are typically shallow and sharply demarcated with a white base and erythematous perimeter. In contrast with other forms of pharyngitis, pharyngeal exudates are typically absent. The presence of generalized rash, usually maculopapular, should also raise suspicion for HIV infection.

Other common features of acute retroviral syndrome are nonspecific and include fever, cervical lymphadenopathy, myalgia/arthralgia, diarrhea, weight loss, and headache (table 4). Symptoms associated with acute HIV infection typically arise about two to four weeks after HIV acquisition. Suspicion for acute HIV infection should be raised in any patient with risk factors for STIs or bloodborne exposures. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Clinical features'.)

●Neisseria gonorrhoeae – The prevalence of pharyngeal gonorrhea is reported to be as high as 15 percent among men who have sex with men (MSM), although the majority of cases are asymptomatic [46-48]. Signs and symptoms of gonococcal pharyngitis are nonspecific and include sore throat, pharyngeal exudates, and cervical lymphadenopathy. Risk factors for STIs, in particular receptive oral intercourse, should raise suspicion for gonococcal pharyngitis. (See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents".)

●Treponema pallidum – T. pallidum, the causative agent of syphilis, is a rare cause of pharyngitis. However, syphilis rates are rising, particularly among MSM and persons with HIV infection [52-54]. Pharyngitis is a common presenting symptom, affecting up to 50 percent of patients with secondary syphilis [55]. Pharyngeal examination often reveals mucous patches on the oral mucosa and tongue (round or oval elevated lesion covered by a pink-gray membrane) (picture 7). Oropharyngeal complaints are rarely the sole presenting symptoms in patients with secondary syphilis. Although symptoms of secondary syphilis vary widely, other common findings include generalized lymphadenopathy and a rash involving the palms and soles. The onset of symptoms typically occurs weeks to months after exposure. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Secondary syphilis'.)

Epstein-Barr virus and other herpes viruses — Acute infection with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, and other members of the herpes virus family including cytomegalovirus (CMV) and herpes simplex virus (HSV) also cause pharyngitis. While the precise incidence and prevalence of symptomatic pharyngitis caused by herpes viruses is not known, rates appear to be highest in adolescents and young adults [56-58].

●Epstein-Barr virus – Pharyngitis is a prominent feature of infectious mononucleosis (the syndrome that can accompany acute EBV infection) and occurs in approximately 85 percent of patients. Other common features include moderate to high fever, marked fatigue, and tender, symmetric posterior cervical lymphadenopathy. Similar to GAS pharyngitis, patchy pharyngeal exudates and palatal petechiae may be present. Tonsillar swelling can be severe. In contrast with other forms of pharyngitis, symptoms caused by acute EBV infection are prolonged, often lasting two to three weeks. Additional distinguishing features include splenomegaly and atypical lymphocytosis (table 5). (See "Clinical manifestations and treatment of Epstein-Barr virus infection" and "Infectious mononucleosis".)

●Cytomegalovirus – CMV can also cause a mononucleosis-like illness. CMV is less likely than EBV to be associated with pharyngitis. The illness is characterized primarily by prolonged fever, less prominent lymphadenopathy, and absent or mild pharyngitis. (See "Infectious mononucleosis", section on 'Cytomegalovirus' and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'CMV mononucleosis'.)

●Herpes simplex virus – Pharyngitis can be the presenting symptom of acute HSV infection, even in the absence of oral ulcers. In a case series of 35 young adults with HSV-1 pharyngitis, the most common findings included pharyngeal erythema and/or exudates and cervical lymphadenopathy [56]. Fever and oropharyngeal ulcers were less common, affecting approximately 35 to 40 percent of patients. Labial and gingival ulcers, which are classically associated with HSV-1 infection, were present in a minority. HSV-2 has also been reported to cause pharyngitis following orogenital contact; symptoms appear to be similar to HSV-1 pharyngitis [59].

Noninfectious causes — The most common noninfectious causes of pharyngitis include allergic rhinitis or sinusitis, gastroesophageal reflux disease, smoking or exposure to second-hand smoke, and exposure to dry air (particularly in the winter). Trauma (eg, caused by tracheal intubation) or vocal strain have also been reported to cause sore throat [60-63].

Medications associated with pharyngitis include angiotensin-converting enzyme (ACE) inhibitors and some chemotherapeutics [60]. Autoimmune disorders that cause pharyngitis include Kawasaki disease, periodic fever with aphthous stomatitis, pharyngitis, and adenitis, and Behçet syndrome.

EVALUATION — The main goals in evaluation of adults with pharyngitis are the exclusion of serious or potentially life-threatening conditions and the identification of treatable causes.

We generally use an algorithmic approach to diagnosis (algorithm 1), which takes into account the relative prevalence of the different causes of pharyngitis and their clinical features (table 1), warning signs for serious or life-threatening conditions (table 6 and table 7), and patient risk factors for sexually transmitted infections (table 3) or other pertinent exposures. (Related Pathway(s): Acute pharyngitis in adults: Evaluation.)

Need for urgent management — Assessing for conditions that require urgent management is an important first step in the evaluation of patients with pharyngitis. Although rare, severe infections of the pharynx and surrounding soft tissue can be life-threatening. Recognizing signs and symptoms of these conditions is critical to management (table 6).

Upper airway obstruction can result from severe pharyngeal inflammation of any etiology but is more commonly associated with infectious mononucleosis and invasive infections involving the deep tissue of the neck. (See "Infectious mononucleosis", section on 'Complications including airway obstruction' and "Deep neck space infections in adults".)

Signs of upper airway obstruction include:

●Muffled or "hot potato" voice

●Hoarseness

●Drooling or pooling of saliva

●Stridor

●Respiratory distress (tachypnea, dyspnea, retractions)

●"Sniffing" or "tripod" positions, which help maintain airway patency

Bacterial invasion of the deep tissue of the neck can lead to infection and/or abscess formation in the peritonsillar, submandibular, parapharyngeal, or retropharyngeal space (figure 2). Suppurative thrombophlebitis (Lemierre syndrome) can arise from bacterial invasion and clot formation of the jugular vein (table 7).

In addition to the signs of upper airway obstruction, features that may indicate deep neck space infections include:

●Severe unilateral sore throat

●Bulging of pharyngeal wall, soft palate, or floor of the oropharynx

●Neck pain or swelling

●Crepitus

●Trismus (irritation and reflex spasm of the internal pterygoid muscle)

●Stiff neck

●Toxic appearance

●Fever and rigors

●History of penetrating trauma to the oropharynx

Patients with signs of airway obstruction generally require urgent airway management and/or hospitalization for additional care. (See "Basic airway management in adults" and "Approach to the adult with dyspnea in the emergency department".)

Most patients with clinical features concerning for deep neck space infection require referral to the emergency department or an inpatient setting for imaging, drainage, and/or surgical consultation and antibiotic treatment. (See "Deep neck space infections in adults".)

Testing for COVID-19 — The need for testing patients with acute pharyngitis for SARS-CoV-2 depends on local prevalence and/or patient exposure. Testing methods and other aspects of diagnosing COVID-19 are discussed separately. (See "COVID-19: Diagnosis".)

Identifying patients with other respiratory viral syndromes — Distinguishing between the two most common infectious etiologies of acute pharyngitis, respiratory viruses and group A Streptococcus (GAS), is important because management strategies differ. Antibiotic treatment is recommended for patients with GAS pharyngitis, whereas supportive care is sufficient for patients with viral pharyngitis.

For patients with symptoms that strongly suggest a viral upper respiratory tract infection, the diagnosis of viral pharyngitis can be made clinically. Features that favor the diagnosis of a respiratory viral syndrome include (table 8 and figure 1):

●Cough (often with fever and malaise)

●Nasal congestion

●Conjunctivitis

●Coryza

●Oral ulcer

●Viral exanthem (picture 1)

Aside from SARS-CoV-2, testing for GAS or other pathogens is not needed, unless the clinical diagnosis is uncertain or risk factors for a specific treatable cause are present (eg, risk factors for sexually transmitted infections).

Determining whom to test for GAS — Patients with a clinical syndrome compatible with GAS pharyngitis who lack symptoms of a respiratory viral syndrome should have microbiologic testing [9,64-67]. Because clinical features of GAS pharyngitis broadly overlap with pharyngitis caused by viruses and other pathogens, empiric treatment for GAS without microbiologic confirmation is generally not recommended.

Clinical features that should raise suspicion for GAS pharyngitis include (figure 1):

●Sudden-onset sore throat

●Fever

●Tonsillopharyngeal and/or uvular edema

●Patchy tonsillar exudates

●Cervical lymphadenitis (often tender and anterior)

●Scarlatiniform skin rash (picture 3) and/or strawberry tongue (picture 4) (scarlet fever)

●History of GAS exposure

When the need for testing is unclear based on clinical features alone, the Centor criteria can help guide the decision to test (table 9). We generally test for GAS pharyngitis in patients with ≥3 Centor criteria (some practitioners use a threshold of ≥2). Patients with Centor criteria <3 are unlikely to have GAS pharyngitis and generally do not need testing [68-70]. Because the Centor criteria have relatively low sensitivity (approximately 50 percent) but high specificity (approximately 82 to 98 percent) [71,72] for the diagnosis of streptococcal pharyngitis, use of these criteria should not replace testing for GAS and should not be used as the determinant of the need for antibiotic therapy.

The Infectious Diseases Society of America and the American Heart Association recommend using clinical judgment to determine who should be tested for GAS [9,64]; by contrast, the European Society of Clinical Microbiology and Infectious Diseases endorse use of the Centor criteria [64]. Recommendations for testing often differ in regions of the world where the prevalence of GAS infection and acute rheumatic fever are higher [73,74]. (See "Society guideline links: Streptococcal tonsillopharyngitis".)

Testing for GAS — For most adults with suspected group A Streptococcus (GAS) pharyngitis, testing with either a sensitive rapid antigen detection test (RADT) or a nucleic acid amplification test (NAAT) is sufficient for diagnosis, and follow-up throat culture is not needed [9]. Because NAATs are highly sensitive and specific, they can also be used as a follow-up confirmatory test when an RADT is negative but streptococcal pharyngitis is still suspected.

For patients with a positive RADT, NAAT, or culture and symptomatic pharyngitis, antibiotic treatment is recommended.

●RADT performance – The specificity of most available RADTs is high, ranging from approximately 88 to 99 percent [9,75]. Thus, in patients with suspected GAS pharyngitis, false positives are uncommon.

For most patients with a negative RADT, additional testing for GAS is not needed. The sensitivity of RADTs in adults ranges from about 77 to 92 percent, varying with the specific assay used [9,75]. In practice, clinicians should refer to the manufacturer's data on sensitivity and specificity when interpreting results. Because the sensitivity of the RADT is moderate in adults, some patients with GAS pharyngitis will be missed when follow-up throat culture is not performed. However, the incidence of complications, such as acute rheumatic fever, is generally low in adults and observational data suggest that using an RADT without culture confirmation is not associated with increased complications [76].

●Confirming a negative RADT in selected patients – We use culture or NAAT to confirm negative RADT results in the following patients [77]:

•Patients who are at higher risk for severe infection or complications from GAS pharyngitis (eg, patients with a history of acute rheumatic fever or immunocompromising conditions)

•Patients who are in close contact with individuals at high risk for complications (eg, patients caring for infants or living with immunocompromised individuals)

•Young adult patients living in college dormitories or other settings where the prevalence of GAS pharyngitis is higher than in the general adult population

•Patients living in areas where acute rheumatic fever is endemic or where there are active acute rheumatic fever epidemics

•Patients in whom clinical suspicion for GAS is high despite a negative RADT (eg, persons with Centor scores ≥3 who have additional risk factors for GAS pharyngitis such as exposure to a person with GAS infection)

Culture generally takes about 24 to 48 hours. With proper collection and processing techniques, the sensitivity of throat culture is between 90 and 95 percent, and specificity is between 95 and 99 percent [9]. We generally do not treat empirically while awaiting results because short delays in therapy have not been associated with higher complication rates. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)

●NAAT performance – NAATs are more sensitive than RADTs and culture, particularly when bacterial burden is low [78]. Their reported sensitivity and specificity is approximately 97 percent and 95 percent respectively, although there is some variability in performance among available assays [79,80]. However, because NAAT are highly sensitive and can detect low bacterial burden, there is risk of false positives (eg, detecting GAS carriage rather than infection) [81]. The false positive rate and its clinical impact (eg, antibiotic overuse) is yet to be determined [82,83].

Specimen collection and transport — The key to optimizing detection of GAS in clinical specimens is appropriate collection and transport of the sample [84]:

●Specimens should be obtained prior to the initiation of antimicrobial therapy in order to maximize diagnostic yield [85,86].

●Specimens should be obtained by vigorous swabbing of both tonsils (or tonsillar fossae in patients without tonsils) and the posterior pharynx. The tongue, buccal mucosa, and hard palate are not satisfactory sites for culture and should be avoided. The importance of obtaining an adequate specimen cannot be overstated, as the sensitivity of both culture and rapid antigen detection testing correlate with inoculum size [87].

●While both RADT and culture are not recommended for most adults, if such a strategy is chosen, two separate samples should be used. The sample obtained for the RADT should not be used for culture. Because GAS remains viable on dry swabs for approximately 48 to 72 hours, samples can be sent for culture after RADT results are obtained.

Assessing risk for HIV and other sexually transmitted infections — Evaluation of the patient with acute pharyngitis should include a sexual history (table 10) and an assessment of other risks for acute HIV infection, such as recent injection drug use or other bloodborne exposures. The two most common sexually transmitted infections that cause pharyngitis are acute HIV infection and gonorrhea.

●Patients with potential exposure to HIV within the past three months who present with pharyngitis, particularly when accompanied with fever, mucocutaneous ulcers, or other signs and symptoms of acute retroviral syndrome (table 4), should be tested for acute HIV infection. When testing for acute infection, we use the most sensitive immunoassay available (ideally, a combination antigen/antibody immunoassay) in addition to an HIV virologic (viral load) test. (See "Acute and early HIV infection: Clinical manifestations and diagnosis" and "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

●Patients with risk factors for sexually transmitted infections, particularly receptive oral intercourse, should be tested for gonococcal pharyngitis. An NAAT for N. gonorrhoeae performed on a pharyngeal swab is the preferred test for gonococcal pharyngitis. If a validated NAAT is not available, culture can also be performed. (See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents", section on 'Patients with extragenital symptoms'.)

●Patients with pharyngitis and risk factors for sexually transmitted infections should also be tested for syphilis, particularly when demographic risk factors are present (eg, men who have sex with men and/or persons with HIV infection). (See "Syphilis: Screening and diagnostic testing".)

In addition to targeted testing for acute HIV infection, gonococcal pharyngitis and/or secondary syphilis, any patient with risk factors for STIs should be screened for STIs based on their gender and demographic risk factors (table 11). (See "Screening for sexually transmitted infections".)

Testing for other pathogens — For the majority of patients with acute pharyngitis, testing for pathogens other than GAS, and SARS-CoV-2 is not needed unless characteristic clinical features or specific risk factors are present, symptoms are prolonged, or a positive result would change management.

As examples, testing for group C or G streptococci, A. haemolyticum, and F. necrophorum can be considered in patients with non-GAS pharyngitis who do not respond to symptomatic therapy within five to seven days [9,88-92]. Routine (aerobic) throat culture can be used to detect group C or G streptococci and A. haemolyticum. F. necrophorum is an obligate anaerobe and requires anaerobic culture conditions. Because infections with these organisms is relatively uncommon and complications are overall rare, testing at the initial visit is generally not recommended [9].

Testing for Epstein-Barr virus and/or cytomegalovirus can be considered in patients with infectious mononucleosis or mononucleosis-like syndromes. While supportive care is the primary treatment for these infections, there is prognostic value in making the diagnosis (see "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Infectious mononucleosis" and "Clinical manifestations and treatment of Epstein-Barr virus infection"). Testing for herpes simplex virus can be considered in patients with severe sore throat, particularly in young adults with characteristic oral or gingival ulcers. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection".)

Rare causes of pharyngitis, such as C. diphtheriae and F. tularensis, can be severe and require prompt treatment. Testing is recommended for patients with compatible clinical syndromes and epidemiologic risk factors. (See "Clinical manifestations, diagnosis, and treatment of diphtheria" and "Tularemia: Clinical manifestations, diagnosis, treatment, and prevention".)

FOLLOW-UP — The great majority of patients who have presumed viral pharyngitis or who test negative for group A Streptococcus (GAS) pharyngitis recover fully within five to seven days without specific treatment [7]. For these patients, symptom relief is the mainstay of care. (See "Symptomatic treatment of acute pharyngitis in adults".)

Patients with GAS pharyngitis usually recover sooner, often within 24 to 72 hours of starting antibiotics. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)

Failure to improve within these time periods should raise suspicion for alternative diagnoses or complications:

●For adults with presumed viral pharyngitis or for those who test negative for GAS and do not improve in seven days, additional evaluation should be performed for previously unsuspected causes, such as infectious mononucleosis, acute HIV infection, A. haemolyticum or F. necrophorum infection, suppurative complications (eg, peritonsillar abscess), or noninfectious causes. (See 'Etiology and clinical features' above.)

●For adults with confirmed GAS pharyngitis who worsen or fail to improve within 72 hours, evaluation for suppurative complications, such as a peritonsillar abscess, or an alternative cause superimposed on chronic GAS carriage should be considered. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Response to therapy'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Streptococcal tonsillopharyngitis".)

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●Beyond the Basics topic (see "Patient education: Sore throat in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Common infectious causes – Acute pharyngitis is one of the most common conditions encountered in outpatient clinical practice. The most common causes of acute pharyngitis are respiratory viruses and group A Streptococcus (GAS). Less common causes include other bacteria, herpes viruses such as Epstein-Barr virus, HIV, and some sexually transmitted infections. (See 'Epidemiology' above and 'Etiology and clinical features' above.)

●Symptoms – Most patients with pharyngitis present with nonspecific symptoms such as a sore throat that worsens with swallowing and cervical lymphadenopathy. Although the etiology of pharyngitis can rarely be determined based on clinical features alone, certain characteristics can help focus the evaluation (table 1). (See 'Etiology and clinical features' above.)

●Approach to diagnosis – When evaluating the patient with acute pharyngitis, we use a systematic approach (algorithm 1) that helps identify patients who can be clinically diagnosed with a respiratory viral syndrome, those who require testing for GAS or other treatable pathogens such as HIV, and those who have severe or life-threatening conditions. The need for COVID-19 testing depends on local prevalence and/or known exposure. (See 'Evaluation' above.)

●Suspicion for viral pharyngitis – For patients with symptoms that strongly suggest a viral upper respiratory tract infection (table 8 and figure 1), the diagnosis of viral pharyngitis can be made clinically after ruling out SARS-CoV-2. Testing for GAS or other pathogens is not needed, unless risk factors for a specific treatable cause are present (eg, risk factors for sexually transmitted infections). (See 'Identifying patients with other respiratory viral syndromes' above.)

●When to test for GAS – Testing for GAS is indicated for patients who have a clinical syndrome compatible with GAS pharyngitis (eg, fever, tonsillar exudates, and cervical lymphadenopathy) and lack features of a viral upper respiratory tract infection (figure 1). When the need for testing is unclear based on clinical features alone, we use the Centor criteria (table 9) to help guide our decision. We generally test for streptococcal pharyngitis in patients with ≥3 Centor criteria. (See 'Determining whom to test for GAS' above.)

●GAS testing methods – Using a sensitive rapid antigen detection test alone is usually sufficient for diagnosis of GAS pharyngitis. Follow-up throat culture is reserved for selected patients who are at high risk for complications, those who are in close contact with persons at high risk for complications, or for persons who live in areas where the prevalence of GAS and/or acute rheumatic fever is high. Nucleic acid amplification tests (NAATs) are increasingly available. Because they are highly sensitive and specific, NAATs can be used in place of a rapid antigen detection test (RADT) or as a follow-up test for patients who have a high suspicion for GAS pharyngitis but test negative by RADT. (See 'Testing for GAS' above.)

●Evaluating for sexually transmitted infections – Evaluation should also include a sexual history (table 10) and assessment of risk factors for HIV. While HIV and sexually transmitted infections are uncommon causes of acute pharyngitis, these are treatable conditions with important public health implications. (See 'Assessing risk for HIV and other sexually transmitted infections' above.)

●Severe disease and complications – Although rare, recognizing signs and symptoms of severe or invasive infections and upper airway obstruction (table 6 and table 7) is a critical part of evaluation. Patients with these signs and symptoms may require urgent stabilization and/or referral to an emergency or inpatient setting for additional care. (See 'Need for urgent management' above.)

●Clinical course – The majority of patients presenting with acute pharyngitis can be clinically diagnosed with respiratory viral syndrome after being ruled out for SARS-CoV-2 and/or will test negative for GAS. These patients typically recover within five to seven days without specific treatment. Patients with GAS pharyngitis usually recover soon, often within 24 to 72 hours of starting antibiotics. Failure to improve within these time periods should raise suspicion for alternative diagnoses or complications. (See 'Testing for other pathogens' above and 'Follow-up' above.)