Case 1: Axillary mass in a First Nations infant

A six-month-old, female, First Nations infant from a northern community was seen by the visiting community physician for assessment of a mass in the right axilla. The child was born at term following an uncomplicated pregnancy, labour and delivery, and had no previous health problems. There were no other symptoms, and growth and development were appropriate. Physical examination was notable for a well-grown, alert and interactive infant with normal vital signs. There was a 2 cm, slightly fluctuant but nontender mass in the right axilla with mild overlying erythema. Examination of the head and neck, respiratory and cardiac systems was normal. There was no adenopathy in the left axilla, the cervical or inguinal regions, and the liver and spleen were not enlarged. An ultrasound was scheduled and showed a single 2 cm × 1.5 cm × 1.2 cm mass with a possibly cystic component. There was slightly increased vascularity in the area surrounding the mass but no other abnormalities. On a follow-up community visit one month after initial presentation, the physician noted a slight increase in the overlying erythema with a possible increase in the size of the mass. The rest of the examination was unchanged and the child remained well and asymptomatic. The lesion was incised and a small amount of purulent fluid was drained. Cultures and smears were sent for testing and the area was packed and dressed. The laboratory subsequently reported the presence of acid-fast bacilli on the smear. An additional detail in the history suggested the diagnosis. The physical examination was also notable for a small scar on the right deltoid area. The child lived in a First Nations community where Bacille Calmette-Guérin (BCG) vaccine was given at birth as part of the regional tuberculosis (TB) control program. Public health records confirmed that the patient was immunized with BCG in the right deltoid area on the first day of life. The child remained well, although the incised lesion drained persistently for 10 weeks before eventually healing with a significant scar. Culture for all species of Mycobacterium was reported as negative after eight weeks of incubation. Mycobacterium tuberculosis is a leading cause of morbidity and mortality worldwide and is considered a disease of poverty (1). It is estimated that more than 8.8 million cases and nearly 1.5 million TB- associated deaths occurred in 2010, of which 95% were in the developing world (1). The rates of TB in Canada have declined significantly since the peak in the 1940s, while the distribution in the population has changed in recent decades (2). TB now occurs mainly in certain geographical areas and high-risk populations. In 2009, foreign-born Canadians accounted for the majority of total cases, while Canadian-born Aboriginals accounted for 21%, a rate nearly six times higher than in the general population. The jurisdiction with the highest rate of TB in 2009 was Nunavut, with 174 cases per 100,000 persons, compared with 4.7 per 100,000 in the general Canadian population (3). BCG is a live, attenuated strain of Mycobacterium bovis. When inoculated, the vaccine induces a mild systemic infection that is intended to confer cross immunity to M tuberculosis (4). Since its introduction in 1921, more than three billion doses of the vaccine have been given. BCG is included in the WHO recommended immunization schedule as part of the WHO TB control strategy (5). Despite its widespread use, there is ongoing controversy as to the effectiveness of BCG immunization. Many of the original studies were conducted in the 1930s to 1950s in different populations using different disease surveillance criteria and different vaccine strains, which gave rise to conflicting results (4). Three meta-analyses of randomized controlled trials and case-control studies investigating newborn BCG immunization found an overall effectiveness of at least 50%, with a protective effect against disseminated disease and meningitis of up to 86% (4). It is important to note that children, and especially infants, typically present with nonspecific signs and symptoms, making the diagnosis of TB challenging. In addition, infants are at greater risk of progression from latent TB to active TB, with potentially severe (meningitis) or disseminated (miliary) disease (6). BCG is used in TB-control programs primarily to prevent miliary disease and meningitis in infants, particularly where access to early diagnosis and treatment may be limited (2). In Canada, the use of BCG is limited to certain high-risk populations, which mainly includes infants from northern Aboriginal communities (2). The vaccine is administered as a single intra-dermal injection of 0.05 mL in the deltoid area of the right arm to newborn infants residing in high-risk communities. The National Advisory Committee on Immunization currently recommends BCG immunization be limited to infants in First Nations and Inuit communities or groups with an average annual rate of smear-positive pulmonary TB of 15 cases per 100,000 over the past three years, or an annual risk of infection of greater than 0.1% if early identification and treatment of TB is not available (2). BCG vaccination is contraindicated for those with immune deficiencies including congenital immunodeficiency and HIV (2). In newborn BCG immunization, it is essential to document negative maternal HIV serology and to establish the absence of a family history of immunodeficiency. BCG vaccination typically results in a local reaction at the injection site, often in the form of a small ulceration, pustule or sterile abscess, beginning three to four weeks after immunization (2). The local reaction does not require treatment and should not be aspirated or incised. Figure 1 shows a typical sterile abscess at the BCG vaccination site, usually the right deltoid area. The local reaction is often accompanied by subclinical regional lymph node enlargement, usually isolated to the ipsilateral axillary lymph nodes but occasionally involving the supraclavicular or cervical regions. In 0.2 to 0.4 per 1000 vaccine recipients, a recognizable lymphadenitis will develop between two to six months following newborn immunization (2). Sterile abscess at the Bacille Calmette-Guérin vaccination site on the right deltoid Severe adverse events associated with BCG vaccination are rare. A report from Canada documented six cases of disseminated BCG resulting in five deaths between 1993 and 2002. All cases were associated with an underlying immunodeficiency, and the five fatalities occurred in Aboriginal infants (7), suggesting a higher risk of disseminated disease in this population when compared with the published medical literature (2). The diagnosis of BCG adenitis is clinical, with the findings of enlarged lymph nodes ipsilateral to the vaccinate site, in the absence of fever, tenderness or constitutional symptoms. Investigations have a limited role, with blood work or chest x-rays having little value. Needle aspiration for microbiology studies may be diagnostic (and possibly therapeutic) but is not required for diagnosis (8). Treatment of BCG lymphadenitis is controversial, because it is generally a benign, self-limited process although the suppurative form can be associated with prolonged drainage and delayed healing (8). Antibiotics and anti-TB drugs, such as isoniazid and rifampin, have been found to be ineffective, and incision and drainage is not recommended (8). Surgical excision is associated with the risks of general anesthetic in young infants and is generally not required (8). In one randomized trial, needle aspiration was shown to result in more rapid healing of suppurative adenitis compared with controls (8) and has been suggested as an effective treatment approach. BCG vaccine continues to be administered as part of the TB-control program in First Nations and Inuit communities at higher risk of TB. In 2009, the rate of TB in the Canadian Aboriginal population was six times the rate in the general population. BCG is contraindicated in immunodeficiency and HIV infection. Nonsuppurative BCG lymphadenitis will resolve spontaneously, while the suppurative form may benefit from needle aspiration.

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