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Bacillus Calmette–Guérin (BCG) vaccine contains a live attenuated strain of Mycobacterium bovis, which provides 64% efficacy against tuberculous meningitis and 78% efficacy against disseminated tuberculosis.1 A number of local adverse reactions are recognised (abscess, suppurative lymphadentitis, keloid formation). An increased number of local complications were reported in the UK and Ireland since the introduction of a new BCG strain in 2002.2 ,3 It is important to distinguish between a normal vaccine response, a local complication and the very rare cases of systemic BCG infection that occur with immunodeficiency. Antibiotics and/or anti-tuberculous medication are rarely needed, except for systemic BCG infection.
Natural history of BCG site
After intradermal injection, BCG multiplies at the inoculation site, then spreads to regional nodes. A normal reaction is a red indurated area, which progresses to a local lesion that may ulcerate 2–3 weeks after vaccination. A crust is formed around this induration for 3–4 weeks. At 6–10 weeks, the crust falls off, leaving a flat 3 to 7 mm scar. Regional lymphadenopathy <1 cm (95% in the axilla) is considered a normal reaction to the vaccine.4 This ‘simple’ lymphadenitis occurs 63 days (range 16–87) after BCG vaccination5 and resolves spontaneously by 9 months.6 Lymphadenitis may be more common when BCG is given to infants <6 months old compared with older children and adults.5
Complications of BCG
Local complications occur in one in a thousand people given BCG vaccine.3 ,7
Injection site abscess
A local abscess (>1 cm in diameter) can develop at the injection site, 30 days (range 4–65) after BCG vaccination.5 Abscess formation is less common when BCG is given to infants less than 6 months old compared with older children and adults. However, abscesses are more likely in infants aged less than 6 months old immunised by untrained vaccinators.5
Suppurative lymphadenitis
About 15% of those with lymphadenitis after BCG develop pus in the node,6 with an incidence of 1 in 1500–2800.3 ,8 Suppuration is more common if BCG is given in the neonatal period. Suppurative nodes tend to burst spontaneously, and can persistently discharge for months.9
Disseminated BCG infection (BCGosis)
Disseminated BCG is defined as ‘BCG infection being present in more than one anatomical site beyond the region of vaccination’.10 Disseminated BCG infection results from severely impaired immunity and occurs in 3.4 children per million given BCG.11 This is associated with primary immune deficiency (severe combined immunodeficiency {SCID}, chronic granulomatous disease or the immune disorders described as ‘Mendelian susceptibility to mycobacterial diseases’), Secondary Immune deficiency (especially HIV infection) or occasionally idiopathic.10 ,12 ,13 BCG disseminates in blood and bone marrow (from where it can be cultured) and spreads to lymph nodes, skin and soft tissues, liver, spleen, lung and/or bone. Mortality from disseminated BCG infection is high (50–71%), reflecting the severe immune deficiency associated with disseminated BCG and the difficulties of antimicrobial treatment.10 ,13
Cardinal features for concern
The key features to identify are those suggesting severe immune deficiency and/or disseminated BCG infection—infection at a site distant to the vaccination site/ draining lymph node. Persistent ulceration at the site of vaccination (with or without lymphadenitis) may also suggest immune deficiency (See box 1).
Key features in the history and examination of children with BCG abscess and lymphadenitis
History
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Is there a family history of immune deficiency (especially SCID)?
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Are there any risks for HIV (did the mother have an HIV test in pregnancy)?
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Are there symptoms of systemic infection (fever, poor weight gain, other opportunistic infections)?
Examination
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Is the child well?
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Local assessment of the lesion and regional lymph nodes; typically these are not hot or tender (‘cold abscess’).
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Assess for evidence of BCG lesions at distant sites (osteitis and skin lesions are the commonest).
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Look for evidence of disseminated BCG disease (fever, other lymphadenopathy, weight loss +/− failure to thrive and hepatosplenomegaly).
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If there are any concerns about disseminated BCG seek advice from a specialist in Paediatric Infectious Diseases and Immunology regarding appropriate investigation and treatment.
Investigations
No investigations are needed for children with local complications of BCG vaccine. Routine bacteriological culture of aspirated pus may identify secondary bacterial infection (mostly staphylococcal). Mycobacterial culture is unlikely to alter management, unless there is a significant risk of tuberculosis. Culture will take a number of weeks to be positive. Molecular methods will then be needed to confirm the organism isolated is BCG.
Infants with suspected disseminated BCG infection will need extensive investigation and should be urgently discussed with a specialist in Paediatric Immunology and Infectious Diseases (consider FBC, CXR and abdominal ultrasound).4
Management
Medical treatment
Anti-tuberculous antibiotics
It is unclear if oral antibiotics (isoniazid, erythromycin or isoniazid plus rifampicin) are effective in the management of the local complications of BCG.14 ,15 This could be due to lack of penetration of antibiotics into an abscess and/or limited antibiotic sensitivity of the BCG strain to antimicrobials (See box 2).16
Specific management of local complications of BCG
Abscess at injection site
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Aspirate pus with a needle (21-gauge), express pus via puncture site. This may be curative. DO NOT INCISE AND DRAIN. Send a swab for routine culture. Other investigations are not routinely indicated.
Non-suppurative (Simple) lymphadenopathy
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If this is the regional node for the BCG site (axillary), reassure parents that this is a normal reaction to BCG vaccination and should resolve without any treatment over the next 9 months. Ask them to return if an abscess develops in the node.
Suppurative lymphadenitis
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Aspirate pus with a needle (21-gauge). DO NOT INCISE AND DRAIN. No medical therapy is advised. Send a swab for routine culture. Other investigations are not routinely indicated.
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If BCG lymphadenitis is persistently fluctuant and suppurative despite aspiration, or has discharged spontaneously, refer for surgical excision. No medical therapy is advised.
Antibiotic sensitivity of the BCG strain
Standard anti-tuberculous drugs (such as pyrazinamide, isoniazid and rifampicin) may have limited effect on BCG. M bovis (and thus BCG) is intrinsically resistant to pyrazinamide. The Danish BCG strain 1331 (currently used in the UK and Ireland) has a minimum inhibitory concentration (MIC) for isoniazid of 0.4 mg/l. ‘Based on criteria set for Mycobacterum tuberculosis, the strain could be considered to be of intermediate susceptibility’ to isoniazid.4 Isoniazid mono-therapy may therefore be of limited use for local BCG complications. Rifampicin resistance can develop in BCG during treatment.16
Prevention of suppuration in lymphadenitis
Antibiotics do not reduce the frequency of suppuration in children with ‘simple’ lymphadenitis after BCG vaccination. A meta-analysis of four randomised controlled trials found no significant difference in the frequency of suppuration between the treatment and control groups for erythromycin or isoniazid.17
Treatment of disseminated BCG
Given the limited effect of antituberculous antibiotics against BCG, expert advice should be sought urgently regarding the appropriate treatment of disseminated BCG infection.4
Surgical treatment
Drainage
Needle aspiration of mycobacterial abscesses reduces the risk of developing a draining sinus compared with incision and drainage. Needle aspiration is thus the treatment of choice for suppurative local complications of BCG vaccination; incision and drainage of BCG complications is not recommended.18
Needle aspiration
Suppurative lymphadenitis can perforate spontaneously leading to sinus formation, which may then discharge for months. Needle aspiration of the abscess in the node reduces the risk of spontaneous drainage.19 Needle aspiration of suppurative nodes also leads to more rapid healing (6.7 v 11.8 weeks) when compared with controls.19 Most infants need just one aspiration, but repeated aspirations may be needed for some, with <5% requiring surgical excision.19 An intranodal injection of isoniazid after needle aspiration may shorten the recovery time, but there is very low quality evidence to support this.14
Surgical excision
Surgical excision of suppurative nodes is likely to be curative and may be needed when needle aspiration has failed or when nodes have already discharged spontaneously with sinus formation.18 The addition of oral antituberculous drugs before or after surgical excision has not been found to be of benefit.20
Test your knowledge
Look at the questions and then select the answer you think is correct from one of the five answers (A to F) below.
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What is the best treatment for non-suppurative (simple) lymphadenopathy?
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BCG is resistant to which antituberculous antibiotic?
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What is the best treatment for BCG injection site abscess?
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Which treatment is best avoided for BCG suppurative lymphadenitis?
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BCG may only have intermediate sensitivity to which antituberculous antibiotic?
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Isoniazid
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Incision and Drainage
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Surgical excision
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Pyrazinamide
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Needle aspiration
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Watchful waiting
The solutions are on page 89.
Answers to the quiz
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(1) F. (2) D. (3) E. (4) B. (5) A.
References
Footnotes
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Contributors AR devised, wrote and edited the article, TC and CB edited the article.
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Competing interests None.
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Provenance and peer review Commissioned; internally peer reviewed.