Practice Essentials
The bacterium now named Arcanobacterium haemolyticum was first described in 1946 as the pathogenic agent causing pharyngitis and cutaneous infections among US service members and indigenous peoples of the South Pacific. [1, 2] As a result of its close resemblance to Corynebacterium pyogenes, some investigators believed the bacterium to be a mutant of this species and appended a subspecies name, C pyogenes subsp hominis.
Based on its peptidoglycan, fatty acid, and DNA characteristics, the bacterium was renamed and reclassified as the first member of the genus Arcanobacterium, which means "secretive bacteria. [3] " Since its original description, the spectrum of diseases caused by A. haemolyticum has been expanded to include invasive infections, including sepsis and osteomyelitis. The importance of A. haemolyticum to dermatology lies in the characteristic rash associated with pharyngeal infection. Interestingly, the cutaneous manifestations of A. haemolyticum infection apparently were not reported in the dermatologic literature until 1996. [4]
Also see Bacterial Pharyngitis.
Presentation
The most common symptoms include the following [5, 6] :
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Sore throat (97-100%)
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Pruritus (33%)
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Nonproductive cough (33%)
In a systematic review of 191 patients with A. haemolyticuminfections, 93.7% of patients reported throat pain. Greater than 50% of cases also presented with tonsillar exudates, fever, and rash.
Pathophysiology
A. haemolyticum is a pleomorphic, facultatively anaerobic, nonmotile, nonsporulating, non–acid-fast, catalase-negative, hemolytic gram-positive rod. However, the organism can demonstrate a variable response to Gram staining if examined after 24 hours of growth. [1, 22, 23] The 70 known strains are divided into smooth and rough biotypes. [24] The smooth biotype predominates in wound infections, and the rough biotype predominates in respiratory tract infections. [25]
The composition of the cell wall is based on lysine, and its fatty acids are primarily straight and monounsaturated. [26] A. haemolyticum ferments dextrose, maltose, lactose, galactose, and glycerol. It coagulates milk and causes liquefaction of gelatin. The bacterium does not reduce nitrates or produce indole. [1]
A. haemolyticum infection has rarely been reported in animals, and its pathogenicity in animals has not been well documented. [27, 28] Humans are believed to be its main environmental reservoir, although A. haemolyticum is not usually a respiratory colonizer.
Since its original description, A. haemolyticum has been occasionally isolated in patients with sepsis, osteomyelitis, septic arthritis, cellulitis, wound infections, necrotizing fasciitis, venous ulcers, skin abscesses, peritonsillar abscesses, cavitary pneumonia, pyothorax, paronychia, omphalitis, otitis media, endocarditis, sinusitis, orbital cellulitis, canaliculitis, meningitis, brain abscesses, diabetic soft-tissue infections, spontaneous bacterial peritonitis, liver abscesses, and chorioamnionitis. [29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 8, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54]
Many of the patients are immunocompromised (eg, from cancer, diabetes). In a 2016 case study, A. haemolyticum was found in not only the wound but also the blood of a diabetic patient presenting with a deep ulcer. [55] Diabetic patients are more vulnerable to infection by A. haemolyticum, and wound and blood cultures are appropriate if the patient appears septic. Multiple wound cultures may be required before A. haemolyticum is identified. A. haemolyticum is sometimes a copathogen with other bacteria, including with Fusobacterium necrophorum in 1 case of Lemierre disease. [56]
Although A. haemolyticum has been implicated in a wide spectrum of diseases, it has been most commonly associated with pharyngitis. Several investigators reported A. haemolyticum as the sole or dominant pathogen in patients presenting with pharyngitis. These studies are limited because the investigators did not look for concomitant infection by viruses or atypical bacteria.
Patients from whom A. haemolyticum is cultured develop specific antibody responses to the bacteria. [18] Furthermore, the bacteria gradually disappear from the oropharynx as the symptoms subside. [1] These studies suggest that A. haemolyticum is a pathogenic organism in some adults with pharyngitis. However, in experimental studies conducted on humans, 325,000 A. haemolyticum organisms were inoculated into each tonsil of 7 healthy volunteers. No organisms could be recovered 1 hour later, but cultures performed 24-48 hours after inoculation showed a predominant growth of A. haemolyticum, which persisted for 4-6 weeks. [1] None of these patients developed symptomatic disease.
Pharyngitis caused by A. haemolyticum must be differentiated from the more prevalent pharyngitis caused by streptococcal organisms. Group A β-hemolytic streptococcus (GABHS) is often the primary cause of bacterial pharyngitis. [57] A. haemolyticum may be missed on routine throat cultures because of the use of rapid group A streptococcal antigen assays and the use of special culture media for optimal isolation of group A streptococcal species. Most cultures for pharyngitis are evaluated at 24 hours, at which point A. haemolyticum colonies are very small and demonstrate minimal hemolysis, and the cultures may be discarded. [20]
Epidemiologic contact studies indicate that the infection is likely spread through an unknown route by human contact with people who are infected. [5] A. haemolyticum is rarely recovered in healthy individuals. [6, 58]
The mechanism responsible for adherence of A. haemolyticum to the pharyngeal mucosa is not known. In vitro experiments have shown that A. haemolyticum does have the ability to invade HEp-2 cells (immortalized upper respiratory tract epithelial cells) and survive there for 4 days, thus creating an intracellular reservoir of bacteria. [59] Gellings and McGee report that the cytolytic action of A. haemolyticum is cholesterol-dependent. A. haemolyticum produces phospholipase D and arcanolysin. Phospholipase D increased the accessibility of cholesterol in the host membrane, and arcanolysin then interacts with that cholesterol, allowing the bacterium to form pores in the host cell. [60, 61]
The pathophysiology of the rash is also unknown; however, the hypothesis that the rash is caused by a bacterial exotoxin is reasonable. Phospholipase D, neuraminidase, and a hemolysin have been identified as extracellular toxins secreted by A. haemolyticum. [62, 63]
Epidemiology
United States
A. haemolyticum has been isolated from the pharynx in 0.4% of adult patients with pharyngitis in the United States. [5] When specifically sought in throat swab cultures, A. haemolyticum is found responsible for 0.5-2.5% of bacterial pharyngitis cases, especially among adolescents. [64]
International
In Canada and Finland, A. haemolyticum pharyngitis has a similar incidence to that found in the United States. In Israel, Czechia, and Sweden, A. haemolyticum was cultured from the pharynx of people with pharyngitis with frequencies of 0.2%, 0.75%, and 2% of patients, respectively. [58, 65, 66, 67, 68]
No known racial susceptibility to the disease has been reported. In 1 study, a higher rate of pharyngitis caused by A. haemolyticum was reported in females than in males, in which the male-to-female ratio was 1:1.6, while another study reported a higher rate in males compared with females, in which the male-to-female ratio was 1.3:1. [6, 69] Pharyngitis caused by A. haemolyticum most commonly affects adolescents and young adults aged 10-30 years, with the maximum incidence occurring among those aged 15-18 years. [65]
Prognosis
The natural course of pharyngitis caused by A. haemolyticum is resolution within a few days to 2 weeks. Antibiotics have been shown to eradicate A. haemolyticum from the oropharynx and to resolve symptoms within 3 days. [5] Whether antibiotic therapy prevents complications in patients with pharyngitis is not known.
Rarely, a patient with pharyngitis caused by A. haemolyticum is hospitalized because of an inability to swallow. Cases of peritonsillar abscess have been reported, requiring drainage in 5 patients. [5, 10, 11] Sepsis developed in 4 patients with pharyngitis; A. haemolyticum was isolated from blood cultures of these patients. [12, 13, 14, 15] Sepsis and pulmonary abscess with tonsillitis developed in 1 patient. [12] No deaths have been reported resulting from pharyngitis caused by A. haemolyticum, although A. haemolyticum caused the death of 2 patients with endocarditis. [33, 44]
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Rash associated with pharyngitis caused by Arcanobacterium haemolyticum. Note the erythematous nature of the rash.
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The rash associated with pharyngitis caused by Arcanobacterium haemolyticum is most prominent on the extremities. Note the rash on the upper limbs.
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The rash associated with pharyngitis caused by Arcanobacterium haemolyticum is most prominent on the extremities. Note the rash on the lower limbs.
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Rash associated with pharyngitis caused by Arcanobacterium haemolyticum. Note the significant involvement of the extremities and the relative sparing of the face.
