The are overprescribed for sore throats in general practice.

Johannes Claassen, MB ChB, MMed (ORL) Senior consultant and full-time specialist, Department of , Universitas Academic Hospital, Bloemfontein Johannes Claassen is currently a full-time senior specialist in the Department of Otorhinolaryngology. He is involved in the full spectrum of general ENT , with special interest in head and cancer surgery.

Correspondence to: Johannes Claassen ([email protected])

The sore throat is one of the most common conditions encountered some of the pressing issues raised by parents. The majority of sore in a general practice and overtreatment is a common occurrence. throats in children are of viral origin. Not only are antibiotics overprescribed, but the antibiotics chosen are often more expensive and of a broader spectrum than needed. The aetiology remains elusive in the majority of cases because of the Although not much has changed over the years a few very basic self-limiting nature of the condition. The frequency of each management principles remain important. varies according to age, season, geographical area and also the immune status of the patient (Table 1). Group A beta-haemolytic The first problem that arises is with the definition of acute remains the major treatable organism and needs a specific work-up. . A spectrum exists from diffuse pharyngeal It also remains the most common bacterial cause of pharyngitis in to inflammation localised to the . The two children and adolescents. terms, acute pharyngitis and acute , are therefore being used synonymously. The differences in evaluating children and adults need to be The anatomy, physiology and embryology of this region need to understood. Pharyngitis in adults is caused by a bacterial be integrated to make a decision about treatment of in this in approximately 5 -10% of patients, while in children bacterial area. What role the tonsils play in the immune system and what the pharyngitis accounts for 30 - 40% of cases.1 Approximately 75% of possible complications of removing them in early might be are adults presenting with a sore throat are prescribed antibiotics for a

Table 1. Aetiology of a sore throat Bacterial Viral Other Group A ß-haemolytic Abscess (peritonsillar, parapharyngeal, retropharyngeal) Groups C,G and F streptococci

Arcanobacterium haemolyticum Para-

Neisseria gonorrhoeae Influenza types A and B Cancer (squamous cell carcinoma, )

Treponema pallidum Human immunodeficiency Autoimmune (Behçet’s disease, benign mucous membrane , )

Chlamydia pneumoniae Adenovirus

Mycoplasma pneumoniae Epstein-Barr virus Postnasal drip

Mycobacterium tuberculosis virus types 1 and 2 Eagle’s syndrome

Francisella tularensis Glossopharyngeal neuralgia

Corynebacterium diphtheriae Crohn’s disease

Yersinia enterocolitica Foreign body

Yersinia pestis Trauma

Trichomonas vaginalis Fungal Protozoa Toxoplasma gondii Candida

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presumed pharyngitis, even though this and continue to be used to perform an method used. Whatever technique is chosen, practice will only help a minority of patients.2 adenotonsillectomy. The must have careful surgical technique is important as well knowledge of all the surgical options available as an awareness of potential complications of Not every sore throat is caused by an infective and must make an informed choice about the the different techniques used. process and not all sore throats are ‘just a cold’. A long list of non-infective causes exists Text box 1. Clinical and epidemiological findings and diagnosis of pharyngitis and these need to be considered as a possible due to group A β-haemolytic streptococci (GABHS) cause in patients not responding to medical management and who have a persistent Features suggestive of GABHS as aetiological agent sore throat (Table 1). Life-threatening • Sudden onset complications can occur and need to be • Sore throat diagnosed and managed early and effectively. • • and abscess formation • Nausea, vomiting, and abdominal pain should be identified and acted on. • Inflammation of and tonsils • Patchy discrete We have also seen shifting trends in throat • Tender, enlarged anterior cervical nodes infection where severe life-threatening • Patient aged 5 - 15 years • Presentation in winter or early spring epiglottitis or supraglotitis affects an older • History of exposure immune compromised group of patients in their late teens or early twenties, needing prompt airway management. This is possibly due to immunisation failures Text box 2. Clinical manifestations of specific organisms in acute pharyngitis against influenzae type B (Hib) and also because the epidemiology of epiglottitis has shifted toward other Rhinovirus causative organisms in the Hib Coronavirus Common cold era.3 The majority of cases of epiglottitis Adenovirus Pharyngoconjunctival fever are thought to be caused by other bacterial Influenza virus Influenza organisms, viral or combined viral- Para-influenza virus Cold, bacterial , and non-infectious Coxsackie virus , hand–foot–mouth disease aetiologies. In addition to Hib, the bacterial organisms responsible for epiglottitis Gingivostomatitis (primary infection) include , other Streptococcus species, , Epstein-Barr virus , Pseudomonas species, Cytomegalovirus Mononucleosis-like syndrome Candida albicans, Klebsiella , Human immunodeficiency virus Acute (primary) infection syndrome Pasturella multocida, and Neisseria species. Bacterial of viruses such as herpes simplex, para-influenzae, Group A streptococci Pharyngitis, scarlet fever varicella zoster and Epstein-Barr also Group C and group G streptococci Pharyngitis results in epiglottitis.3 Red flags in these Mixed anaerobes Vincent’s angina (necrotising gingivostomatitis) patients would be progressively worsening Fusobacterium necrophorum Lemierre’s syndrome (septic thrombophlebitis symptoms and neck swelling. Lemierre of the internal jugular vein) syndrome, which is a severe suppurative Arcanobacterium haemolyticum Pharyngitis, scarlatiniform rash of bacterial pharyngitis, needs Pharyngitis to be considered.4 Treponema pallidum Secondary syphilis Pharyngeal Finally, when surgery is contemplated, it is Corynebacterium diphtheria Diphtheria very important to do a proper preoperative Pharyngitis, enterocolitis assessment. The surgeon needs to know the indications for an adenotonsillectomy and be Mycoplasma pneumoniae , pneumonia able to handle the potential complications and, Chlamydophila pneumoniae Bronchitis, pneumonia more importantly, know how to avoid them. Chlamydophila psittaci psittacosis Many techniques have been described

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Anatomy of a sore throat, , fever and of age but can occur in children younger Waldeyer’s ring, a ring of lymphoid tissue erythema of the pharyngeal mucosa with than 3 and in adults older than 50.5 Acute in the pharynx, is formed by the palatine enlarged tonsils. There is normally not symptoms include: dry throat, , tonsils, as well as the pharyngeal tonsils an exudate present, as would be seen with fever, odynophagia, dysphagia, otalgia, (), tubal tonsils and lingual certain bacterial pharyngitis. headache, body aches and pains and cervical tonsils. The arterial supply to the tonsils (text box 2). is extensive and comes from the external Coxsackie virus causes small vesicles to carotid system. The main supply enters form with erythematous bases that can Examination of the mouth and pharynx the inferiorly from three separate ulcerate and spread over the anterior may reveal a dry tongue and enlarged tonsils arteries: tonsillar pillars, and pharyngeal wall. with yellowish white spots on the tonsils. • tonsillar branch of the dorsal lingual Herpes simplex virus is normally associated A membrane or purulent may artery with a ‘cold sore’. It affects older children and be present over tonsils or pharynx.5 When • ascending palatine artery young adults, and may cause exudative or symptoms that include coughing, diarrhoea, • tonsillar branch of the facial artery. non-exudative pharyngitis. conjunctivitis and coryza are present, a viral aetiology is more likely. With other Venous drainage is through the Epstein-Barr virus (EBV) infection is non-infective causes of pharyngitis (reflux, peritonsillar venous plexus to the lingual important for two characteristic clinical postnasal drip, cancer, fungal infections, and pharyngeal veins. The nerve supply to traits. Firstly, it can lead to very rapid cigarette smoke), the aetiology is normally the tonsillar region is via the branches of enlargement of tonsils (sudden onset of identifiable and can be treated or avoided. the glossopharyngeal nerve and branches in patient with large dirty-gray of the lesser palatine nerves. Lymph from tonsils). Petechiae at the junction of the hard Approach to a patient with a the tonsillar area drains primarily to the and soft palate may be present. The airway sore throat jugulodigastric nodes. obstruction may be life-threatening and The principles for diagnosing a patient rest on should be managed promptly. Secondly, it taking a good history followed by a complete Presentation of a patient with can lead to the formation of a maculopapular examination. Some specific symptoms and pharyngitis rash in a large percentage of patients who signs may reveal the identity of certain Viral are given penicillin (as high as 95%), even organisms but in most cases it only presents A viral pharyngitis usually presents with if no previous incidents of reactions against as a general sore throat (Algorithm 1). mild symptoms, most patients complaining penicillin are documented. The decision to treat with antimicrobials Influenza is readily transmitted and remains a difficult one despite the available therefore of epidemiological importance. special investigations, and most decisions The sore throat associated with influenza are still made on clinical findings. may be distinguished from streptococcal This unfortunately leads to massive pharyngitis by several features: overtreatment of patients with antibiotics. • the presence of influenza cases in the Listen to the patient – if the symptoms community () initially improved and then worsened • association with (2nd time sicker), it may indicate an initial • . viral infection that became complicated by a secondary bacterial infection, which Bacterial normally happens after 7 - 8 days. Group A β-haemolytic Streptococcus (GABHS) is the most common cause GABHS remains the most prominent of acute bacterial pharyngitis. Acute pathogen requiring treatment in patients rheumatic fever and glomerulonephritis of all ages, so the decision is whether or not are part of the autoimmune-mediated the pharyngitis is attributable to group A group of complications due to group A streptococci. Streptococcus infection and can occur after a latent period of 2 - 3 weeks. Acute Other that may require specific rheumatic fever presents with various treatment are: manifestations that may include carditis, • EBV mononucleosis (splenic enlarge- chorea, arthritis, subcutaneous nodules and ment and airway obstruction) erythema marginatum. GABHS infection • non-group A streptococci (confirmed by has a peak incidence at about 5 - 6 years culture)

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Algorithm 1. Approach to a patient with a sore throat.

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antibiotics. Unfortunately even one prior dose of antibiotics may result in a negative test. It is highly specific but not as sensitive as a throat culture, which remains the gold standard, although results are delayed.6 Proper collection (vigorous swabbing of tonsils and posterior pharyngeal wall) and transport of the sample are key to making a correct diagnosis. If the rapid test is negative it should be followed by a throat swab for culture if streptococcal tonsillitis is strongly suspected. This, however, might lead to over-treating because it is difficult to reliably differentiate between acute and chronic infection from a throat culture.

Reasons to treat GABHS: • to prevent post-streptococcal sequelae − acute rheumatic fever is a significant problem in developing countries • to prevent suppurative complications − , and • to reduce symptoms − there is a modest (approximately one day) reduction in symptoms with early treatment Algorithm 2. Evaluation of adenotonsillar hypertrophy. and for patients with more severe symptoms it might be two and a half days • influenza virus (high-risk patient with (severe symptoms ≥3 )7 severe symptoms) • to prevent transmission − while this is • primary HIV infection important in paediatrics, due to extensive • N. gonorrhoeae. exposures, it is considered far less important in adults. Diagnosis of acute GABHS tonsillitis Management of a sore throat Most cases are diagnosed clinically, and Symptomatic management the Centor criteria are based on clinical The primary decision in these patients is evaluation of symptoms and signs. It is widely whether to give antibiotics and to treat the used and accepted. The four criteria are: specific underlying aetiology, e.g. reflux. • tonsillar exudates If no antibiotics are given treatment is • tender anterior cervical adenopathy symptomatic. Basic principles remain: • fever by history • rest • absence of coughing. • adequate fluid intake • The presence of 3 - 4 of the criteria has a • . positive predictive value for GABHS of 40 - 60%. The absence of 3 - 4 of the criteria has Systemic treatment options include negative predictive value of 80%. antimicrobial agents, pain and possibly anti-inflammatory agents. The use A rapid antigen test for GABHS has been of remains controversial developed which has helped the decision and the benefit may be limited to infectious whether or not to treat patients with mononucleosis.

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Algorithm 3. Management of post- bleeding.

The local or topical treatment options Antimicrobial management of Penicillin include: streptococcal pharyngotonsillitis Penicillin has a particularly narrow spectrum • lozenges The current guidelines for the management of activity and also lacks the resistance by • sprays of upper infections in GABHS. Resistance in the macrolide group • oral rinses (gargles) South Africa should be applied. is associated with excessive use. • alternative .

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Table 2. Indications for adenotonsillectomy Tonsillectomy Infection More than 6 episodes of acute recurrent Purulent adenoiditis tonsillitis or 3 episodes per year for 2 years or hypertrophy associated with: longer • chronic recurrent acute Recurrent acute tonsillitis associated with: • chronic middle-ear effusions • cardiac valvular disease • chronic otitis media with perforations of • recurrent febrile convulsions tympanic membranes Chronic tonsillitis associated with: • chronic otorrhea halitosis • persistent sore throat • cervical adenitis with tenderness Peritonsillar abscess Mononucleosis with obstructive symptoms not responding to medical treatment

Obstruction Obstructive sleep apnoea or excessive snoring Obstructive sleep apnoea or excessive snoring Chronic mouth Chronic Complications present of adenotonsillar Adenotonsillar hypertrophy associated with hypertrophy: complications of obstructions: • cor pulmonale • cor pulmonale • failure to thrive • failure to thrive • dysphagia • dysphagia • speech abnormalities • speech abnormalities • craniofacial growth abnormalities associated • craniofacial growth abnormalities with occlusion abnormalities associated with occlusion abnormalities

Other Suspected neoplasia Suspected neoplasia Chronic sinusitis associated with

Children Children • Penicillin VK: 250 mg twice daily for 10 • <30 kg: amoxycillin, 750 mg once daily days (<27 kg); 500 mg twice daily for 10 for 10 days days (>27 kg) (given 30 minutes before • >30 kg: amoxycillin 1 500mg once daily food) for 10 days. • Benzathine penicillin as intramuscular injection: 3 - 5 years: 600 000 U; >5 Adults years: 1.2 MU • Amoxycillin, 500 mg twice daily for 10 days

Adults and adolescents Short-course • Penicillin VK, 500 mg twice daily for 10 This is a recent development. Adam and days (given 30 minutes before food) colleagues showed equivalence between • Benzathine penicillin (intramuscular penicillin given 3 times daily for 10 days injection): 1.2 MU as single dose. and a number of regimens (including use of new macrolides or second-generation To minimise the discomfort of parenteral ) given for 5 days.8 administration, the medication should be given at room temperature. For patients Children receiving 1.2 million U, 300 000 U can be • Amoxycillin-clavulanate 40 mg/kg/day given as procaine penicillin.11 in 3 divided doses • Azithromycin 10 - 20 mg/kg once daily Amoxycillin for 3 days Can be used as an alternative to penicillin • Clarithromycin 7.5 mg/kg twice daily VK. If patients infected with Epstein-Barr • Cefpodoxime 4 mg/kg twice daily virus are treated with amoxicillin, a rash • Cefprozil 7.5 mg/kg twice daily might occur. • Cefuroxime 10 mg/kg twice daily.

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Adults correlated with various degrees of sleep- Consider non-infectious causes of sore • Amoxycillin-clavulanate 375 mg 3 times disordered breathing.13 However, there is throat (e.g. gastro-oesophageal reflux daily limited literature on diminished symptoms disease, chronic irritation from cigarette • Azithromycin 500 mg once daily for 3 after adenotonsillectomy. Enuresis is smoke, alcohol or hay fever). days another indicator that there might be • Clarithromycin (modified release) 500 severe underlying obstructive sleep apnoea References available at www.cmej.org.za mg once daily symptoms. • Cefpodoxime 100 mg twice daily • Cefprozil 500 mg twice daily Indications for • Cefuroxime 250 mg twice daily adenotonsillectomy • Telithromycin 800 mg once daily. Tonsillectomy or adenotonsillectomy is a In a nutshell surgical procedure that can cause serious • It is important to understand the possible Chronic adenotonsillar complications and therefore the indications underlying aetiology involved in a sore throat, both infective and non-infective hypertrophy for surgery need to be considered with causes. The most important decision re- The various degrees of airway obstruction caution (Table 2). volves around antibiotics, and the ques- that are caused by adenotonsillar hypertrophy tion to give or not to give remains a daily challenge for most practitioners. are currently the most common indication Possible complications of 9 • A good history is the most important part for an adenotonsillectomy in the USA. adenotonsillectomy of your assessment. Explaining the differ- Great loads of occur Postoperative haemorrhage is the most ent possibilities to the patient or parents in hypertrophied and chronically infected common and most serious complication normally helps them understand the need 10,11 to withhold or to give antibiotics tonsils. It is important to note that second- of adenotonsillectomy. Rates vary from • If there is an indication for surgery, be hand smoke is also listed as a cause for 0.5% to 10%. This can be prevented by a sure to clarify your indication to the par- adenotonsillar hypertrophy (Fig. 1). good preoperative assessment focusing on ents or patient. medication usage and possible coagulation • Know your anatomy and be sure to follow sound surgical principles. Know how to abnormalities, a thorough knowledge of the manage the possible complications of ad- anatomy, and meticulous attention to intra- enotonsillectomy and, more importantly, operative haemostasis (see algorithm 3). know how to prevent them!

Other complications include injury to the teeth or , airway obstruction and pulmonary oedema, velopharyngeal insufficiency, nasopharyngeal stenosis and cervical spine stenosis.

Fig. 1. Adenoids obstructing posterior Persistent sore throat choanae. It is important to reconsider the initial diagnosis. Consider an alternative diagnosis The importance of this condition rests on or further investigation if the individual has prevention of the possible serious complica- not responded to a course of antibiotics. tion that can be caused by obstructive sleep Consider a neoplasm if the sore throat is apnoea, namely persistent, especially if there is a neck mass. and cor pulmonale, failure to thrive and de- velopmental delay.12 Behavioural problems Indications for urgent referral include: in these children are common, particularly • an unexplained persistent sore or painful attention deficit hyperactivity disorder (see throat −‘persistent’ refers to a time frame algorithm 2). of 3 - 4 weeks • red, or red and white patches, or These findings have been well correlated ulceration or swelling of the oral/ with formal sleep study results. Not all pharyngeal mucosa for more than 3 children need to have a polysomnograph weeks done and not all children tested have • odynophagia or dysphagia for more than positive results. In various different studies 3 weeks the association between behavioural and/ • unexplained hoarseness accompanied by or academic problems has been well persistent sore throat.

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