Arcanobacterium haemolyticum

Epidemiology

Humans are the primary reservoir of A. haemolyticum , where the organism is found in the pharynx and on the skin. A. haemolyticum has been implicated increasingly in association with pharyngitis (reported incidence of 0.3%–9.3%) and rash in older children and young adults, with an increased incidence rate, reported among adolescents of 15–18 years of age. Multiple case reports document infection at pulmonary and extrapulmonary sites. A slight predominance in girls and women is noted among reported pharyngitis series, but a male predilection is noted in systemic A. haemolyticum infections. ^, Transmission occurs from person to person purportedly by droplet transfer ; the incubation period is uncertain.

Microbiology, Pathogenesis, and Virulence

A. haemolyticum is a gram-positive or gram-variable, pleomorphic, nonmotile, nonsporulating bacillus. It appears strongly gram positive in young cultures and becomes gram variable after 24 hours. Optimal growth occurs in human or rabbit blood agar and is enhanced in carbon dioxide; after 48 hours of incubation, colonies on horse or sheep blood agar (the preferred medium for throat cultures) are small (0.1–0.5 mm), with a narrow zone (1 mm) of hemolysis. A black, opaque dot appears at the center of each colony, and a tiny, dark pit remains if the colony is scraped aside. In clinical isolates, smooth and rough colony biotypes have been noted. Smooth colonies are β-hemolytic, β-glucuronidase negative, and predominately observed in wound infections. Rough colonies are weakly β-hemolytic to non-hemolytic, β-glucuronidase positive, and are primarily associated with respiratory tract infections. A. haemolyticum resembles Corynebacterium diphtheriae on Löffler medium, whereas poor growth on tellurite medium and lack of catalase distinguish A. haemolyticum . The organism also ferments glucose and maltose, usually within 4 days. Cross-reaction with streptococcal serogroup B specific antiserum can occur. ^, Many cases of A. haemolyticum pharyngitis can go undetected because of the slow growth (≥72 hours) in culture and if streptococcal antigen testing or nucleic acid amplification tests are performed without a backup throat culture.

The pathogenesis of A. haemolyticum is not well characterized. Production of phospholipase D, a dermonecrotic toxin, has been demonstrated. A cholesterol-dependent cytolysin, designated arcanolysin, has also been identified. These factors may play an important role in the adherence and invasion of A. haemolyticum into non-phagocytic cells.

Clinical Manifestations

A. haemolyticum is reported most frequently in association with pharyngitis in people between 10 and 30 years old. Most patients complain of mild fever and sore throat. Some have persistent or recurrent pharyngeal symptoms for weeks before diagnosis. Pharyngeal erythema is present universally, and tonsillar exudate is common, occurring in up to 70% of cases. Membranous pharyngitis mimics diphtheria. Lymphadenopathy occurs in 26%–81% of reported patients, primarily involving the anterior cervical or submandibular lymph nodes bilaterally.

An associated rash (only in patients with pharyngitis) was noted in 23%–75% of cases reported, most frequently involving the extensor surfaces of the extremities, the neck, and trunk; face, palms, and soles typically are spared, although a case report describes vesicular lesions of the palms and soles. The exanthem, commonly described as a scarlatiniform rash (erythematous, blanching fine papules), usually develops 1–4 days after the onset of sore throat, although rash has been noted before the development of pharyngitis. Pruritus occurs in approximately 50% of patients, urticaria and erythema multiforme have been described. Mild desquamation of the skin on the hands and feet follows illness.

In both healthy and immunocompromised hosts, A. haemolyticum is the cause of sporadic invasive infections, including septicemia, endocarditis, septic emboli, jugular vein thrombosis (Lemierre syndrome), peritonsillar abscess, paravertebral abscess, meningitis, brain abscess, pneumonia, pleural effusion, sinusitis, urinary tract infections, pelvic abscess, spontaneous bacterial peritonitis, and bone and joint infections. Cellulitis, cutaneous abscesses, skin ulcers, and wound infections have been reported. ^{, , ,} Chorioamnionitis caused by A. haemolyticum was reported in a 19-year-old mother who delivered a healthy infant. Endocarditis complicated by cerebral emboli was described in a young woman with congenital heart disease. Thyroid abscess was reported in a 2 year old patient. Orbital cellulitis caused by A. haemolyticum is uncommon, but is well described in children, ^, and a case of orbital necrotizing fasciitis and osteomyelitis complicating ethmoid sinusitis in an adolescent has been reported. Septicemia has been reported rarely in adolescents with concurrent Epstein-Barr virus infection. ^, Subdural empyema and bacteremia following head trauma has been reported in an adolescent.

Coinfection of A. haemolyticum with a variety of other bacterial pathogens can occur in wound, respiratory tract, intra-abdominal, and skin and soft tissue infections. ^{, , , , , , ,} A. haemolyticum has been isolated from the bloodstream of patients in combination with other bacteria including Fusobacterium necrophorum, streptococci , and Bacteroides species. ^{, , , ,}