What Caused Cough and Hemoptysis in a Patient Recently Treated for Exudative Tonsillitis?

February 21, 2008
Russell W. Steele, MD
Russell W. Steele, MD

,
Kavita Prabhakar, MD
Kavita Prabhakar, MD

,
Thomas M. File, Jr, MD
Thomas M. File, Jr, MD

,
Katherine L. Baumgarten, MD
Katherine L. Baumgarten, MD

A 22-year-old man presentedwith a 3-week history ofcough and hemoptysis withright-sided chest pain and decreasedoral intake associated with a 4.5-kg(10-lb) weight loss. Ten days beforehospital admission, he was involvedin a fistfight, which resulted in his arrest.He was taken to jail and placedin a holding cell for 3 hours. Shortlybefore his pulmonary symptoms developed,he was seen by his primarycare physician because he had a sorethroat and exudative tonsillitis, forwhich amoxicillin/clavulanate wasprescribed. He stopped taking theantibiotic after 3 days.

A 22-year-old man presentedwith a 3-week history ofcough and hemoptysis withright-sided chest pain and decreasedoral intake associated with a 4.5-kg(10-lb) weight loss. Ten days beforehospital admission, he was involvedin a fistfight, which resulted in his arrest.He was taken to jail and placedin a holding cell for 3 hours. Shortlybefore his pulmonary symptoms developed,he was seen by his primarycare physician because he had a sorethroat and exudative tonsillitis, forwhich amoxicillin/clavulanate wasprescribed. He stopped taking theantibiotic after 3 days.

The patient's medical history wassignificant for childhood asthma andwhooping cough. He underwent anadenoidectomy at age 5 years andan inguinal hernia repair at age 11months. He works as a mechanicand lives with his mother. Each day,he smokes half a pack of cigarettesand drinks two 24-oz bottles of beer.

In the review of systems, it wasdiscovered that in the 3 weeks precedingthis visit, the patient had fairlysevere myalgia, weakness, and fatigue.He takes no medications andhas no known drug allergies. Thereis no history of sick contacts, tuberculosisexposure, or recent travel,and there are no pets in the patient'shousehold.

On presentation, his temperaturewas 39.1C (102.4F), his pulse ratewas 100 beats per minute, his respirationrate was 22 breaths perminute, and his blood pressure was120/70 mm Hg. His weight was 58.5kg (129 lb). He had good dentitionand oral hygiene. His posteriororopharynx was markedly erythematous,and no exudate was noted.Wheezing was heard in the rightupper lung field. All other findingsfrom the physical examination werenormal.

Initial laboratory studies yieldedthe following results: white bloodcell (WBC) count, 9730/mu;L, with65% segmented neutrophils, 13%lymphocytes, 8% monocytes, and4% eosinophils (this WBC count wasdecreased from 14,000/mu;L, whichwas recorded 21 days earlier); hemoglobinlevel, 11.7 g/dL; hematocritvalue, 36.3%; platelet count,242,000/mu;L; C-reactive protein level,15.1 mg/L; and erythrocyte sedimentationrate, 86 mm/h. Findingsfrom a complete metabolic panelwere essentially within normal limits.Aurinalysis revealed trace leukocytes,protein, and blood. A urinedrug screen was positive for opiatesand cocaine.

Findings from both a chest radiographand a CT scan of the chest indicateda thick-walled cavitary lesionin the right chest.

DIFFERENTIAL DIAGNOSIS

Dr File: I would want to examine thepatient's sputum early in the courseof management, since doing somight quickly reveal the cause of illness.He has a lung abscess that ismost likely the result of aspiration,perhaps related to his altercation andalcohol intake. Such infections inyounger persons are most often caused by a mix of aerobic andanaerobic bacteria. This is particularlytrue in persons with poor oral hygiene,which was not the case for ourpatient.

Tuberculosis or, less commonly, anontuberculosis mycobacterial infectionshould be considered in patientswith cavitary lung disease. A significanthilar adenopathy suggests theinvolvement of fungal or mycobacterialorganisms. I would suspectcoccidioidomycosis if he had a compatibletravel history. Aspergillus cancause cavitary lung disease, producinghemoptysis, but this occurs almostentirely in patients with significantunderlying conditions.

Histoplasma occasionally causescavitary lung disease. I also wouldinclude actinomycosis and nocardiosisin the differential diagnosis, bothof which can produce cavitary lesions. Legionella can cause these lesions,although rarely; however, Iwould expect a more progressivecourse if it was the involved organism.In light of the patient's historyof tonsillitis, group A β-hemolyticstreptococcus infection can be considered,but this diagnosis is low onmy list because I would expect amore progressive disease courseand possibly an empyema. In allcases of community-acquired pneumonia,community-onset Staphylococcusaureus infection, which hasbeen associated with cavitary pneumonia,must be considered. Beingin jail is a risk factor for community acquiredpneumonia, but the patientwas only there for a few hours,which may or may not be of consequenceto his illness.

To recap, I would want to examinethe patient's sputum to identifypredominant organisms and to helprule out fungal and mycobacterialcauses of illness. If examination ofthe sputum is not helpful, a bronchoscopyto obtain optimal culturespecimens would be my next step.

HOSPITAL COURSE

Results of initial laboratory tests forHIV, Epstein-Barr virus,

Strongyloides

,and

Cryptococcus

were negative.Apurified protein derivative tuberculinskin test was nonreactive. Thepatient was initially treated withvancomycin and piperacillin/tazobactam.On hospital day 3, he underwentbronchoscopy; Gram stain ofbronchoalveolar lavage (BAL) fluidfrom the upper lobe revealed numerouspolymorphonuclear leukocytes,Gram-positive rods, and Gram-positivecocci in clusters. Culture of theBALfluid yielded a heavy growth of

Arcanobacterium haemolyticum

.

Intravenous piperacillin/tazobactamwas continued for 6 days, andthe patient was discharged home ona regimen of moxifloxacin to completea total of 14 days of antimicrobialtherapy. A chest radiograph 1month later showed almost completeresolution of the pulmonaryabscess.

FINAL DIAGNOSIS

Infection caused by Arcanobacteriumhaemolyticum

DISCUSSION

A haemolyticum, formerly known asCorynebacterium haemolyticum, colonizesskin and mucous membranesof healthy persons. It was first describedin 1946 as an occasionalcause of exudative pharyngitisand skin infections.1 It is a pleomorphic,Gram-positive, catalase-negative,nonmotile rod.

A haemolyticum is an occasionalcause of tonsillitis and pharyngitis.Itaccounts for 0.4% to 1.4% of all casesof pharyngitis in adolescents andyoung adults; its maximum impactis in 15- to 18-year-olds, in whom itaccounts for 2.5% of all cases ofpharyngitis.2 The pathogenesis of A haemolyticum infection is not completelyunderstood, but the organismproduces biologically active toxins,including ? hemolysin andphospholipase D, which is a lipidhydrolyzingenzyme capable ofdamaging cell membranes. A haemolyticumexhibits a synergistic effectwith other pathogens in causing tissuedamage.

The signs and symptoms of pharyngitiscaused by Ahaemolyticum aresimilar to those caused by infectionwith group Astreptococci; an exceptionis that up to two thirds of patientswith A haemolyticum infectionmay have a nonproductive cough.3Up to 70% of patients with A haemolyticuminfection have a scarlatiniform-like rash without circumoralpallor.4 Compared with the rash ofscarlet fever, the rash of A haemolyticuminfection is characterized bymore discrete lesions and the skindoes not desquamate, which is similarto the rash of Epstein-Barr virusinfection.

There are numerous case reports of deep-seated infections caused byA haemolyticum with and withoutbacteremia. Among 8 patients aged33 to 87 years who were immunocompromisedor who had knownrisk factors for the infection, 2 hadbacteremia secondary to wound infectionand 6 others had bacteremiawith no identifiable source.5 Anothergroup of 8 patients, aged 15 to 30years, were immunocompetent, although1 patient was receiving corticosteroidtherapy because of concurrentEpstein-Barr virus infection.4Six of these patients had tonsillitis orsinusitis as the site of infection. Another7 patients had deep-seated infectionswithout bacteremia, 6 ofwhich were caused by multiple organisms,5 by anaerobic bacteria,and 1 by Streptococcus milleri.4 Twopatients had concurrent Epstein-Barrvirus infection.

Three patients have been describedwith endocarditis. One wasan 87-year-old previously healthyman who had fatal septicemia with native bicuspid aortic valve endocarditis.2 Another case involved a 50-year-old injection drug user who hadmitral valve endocarditis resultingin cerebral emboli and death.6 Thethird patient was a 33-year-old HIV-positiveinjection drug user who hadtricuspid valve endocarditis with apulmonary embolus in his rightlower lobe; this patient experiencedfull recovery and had no relapsesduring 4 months of follow-up.6Treatment of endocarditis requires2 antibiotics that are active againstthe causative organism, such as ampicillin/gentamicin or vancomycin/gentamicin in the case of A haemolyticuminfection.

There are 6 reported cases ofmeningitis, 3 of which were causedby mixed bacteria and 1 of whichwas caused by anaerobic bacteria.7Two of these cases involved Bacteroidesspecies, and 1 involved Fusobacteriumnecrophorum. Managementrequires aspiration of the abscessand long-term therapy withpenicillin G.

Pulmonary infection is also wellreported. A pulmonary abscess developedin a patient with tonsillitis,which was similar to our case, andwas successfully managed witherythromycin, dibekacin, and metronidazole.8 Pulmonary infectionwith empyema developed in a womanwith breast cancer, and right lowerlobe pneumonia with bilateral effusionsdeveloped in a previouslyhealthy 20-year-old man.8 The organismsidentified in the latter patientwere Ahaemolyticum, Mycoplasmapneumoniae, and an unidentifiedanaerobic Gram-positive coccus.Other reported infections that involveA haemolyticum are paravertebralabscesses, osteomyelitis, sinusitis,and abscesses with cellulitis.2

Diagnosis of Ahaemolyticum infectionis made by culture, which requireshuman or rabbit blood agarrather than sheep blood agar foridentification. The colonies are smalland white. Most throat cultures areplated on sheep blood agar and areread at 24 hours. Thus, A haemolyticumis usually missed. This organismis differentiated from streptococcalspecies by morphology,from Corynebacterium species by beta;hemolysis and its being negative forcatalase production, and from Actinomycesby a lack of proteolytic activityand failure to ferment xylose.

A haemolyticum is susceptible tomany antibiotics, including macrolides,penicillins, clindamycin, vancomycin,ciprofloxacin, and tetracycline.It is likely that azithromycinand clarithromycin are also effective.Current treatment recommendationsare to use high doses of parenteralpenicillin combined with an aminoglycosidefor moderate to severe disease.2 Broad-spectrum β-lactamantibiotics, clindamycin, and macrolidesare equally effective.2 Manyexperts prefer macrolides because oftheir success when used after treatmentfailure with beta;-lactam agents.

When drug penetration might becompromised, such as in osteomyelitisor endocarditis, macrolides orclindamycin plus rifampin are preferredover beta;-lactam antibiotics.Clinical failures have occurred withpenicillin, while erythromycin hasbeen consistently effective.2

References:

  • MacLean PD, Liebow AA, Rosenberg AA. A haemolytic Corynebacterium resembling Corynebacterium ovis and Corynebacterium pyogenes in man. J Infect Dis. 1946;79:69-90.

  • Waagner DC. Arcanobacterium haemolyticum: biology of the organism and diseases in man. Pediatr Infect Dis J. 1991;10:933-939.

  • Chen Y, Colodner R, Chazan B, Raz R. Pharyngotonsillitis due to Arcanobacterium haemolyticum in northern Israel. Isr Med Assoc J. 2005;7: 241-242.

  • Miller RA, Brancato F, Holmes KK. Corynebacterium hemolyticum as a cause of pharyngitis and scarlatiniform rash in young adults. Ann Intern Med. 1986;105:867-872.

  • Robinson BE, Murray DL. Corynebacterium hemolyticum and pharyngitis. Ann Intern Med. 1987;106:778-779.

  • Worthington MG, Daly BD, Smith FE. Corynebacterium hemolyticum endocarditis on a native valve. South Med J. 1985;78:1261-1262.

  • Altmann G, Bogokovsky B. Brain abscess due to Corynebacterium haemolyticum. Lancet. 1973;1: 378-379.

  • Waller KS, Johnson J, Wood BP. Radiological case of the month. Cavitary pneumonia due to Arcanobacterium hemolytic. Am J Dis Child. 1991; 145:209-210.