Management of Bacillus Calmette-Guérin Lymphadenitis
Bacillus Calmette-Guéin (BCG) related regional lymphadenitis is not an uncommon complication following BCG vaccination. We present a case series of 11 infants with suppurative BCG lymphadenitis managed in Hospital Authority Infectious Disease Centre of Hong Kong over a 5-year period. All of them presented with isolated left axillary mass which suppurated at a mean of 3.5 months (range 2 to 5 months) after BCG vaccination. The diagnosis of the condition is basically clinical. Five infants who were initially managed with needle aspiration alone showed significant regression in the sizes of their enlarged lymph nodes and surgical excision was spared. Surgical incision and drainage was performed in 5 other infants prior to referral to our centre. They all developed significant irregular scarring and 2 eventually developed keloids over their scars upon healing. We recommend that suppurative BCG lymphadenitis should be managed initially by needle aspiration. Total excision should be considered if aspiration fails or suppuration recurs despite repeated needle aspiration. Incision and drainage is mentioned to be condemned.
Keyword : Bacillus Calmette-Guéin (BCG); Lymphadenitis; Management
The live attenuated Bacillus Calmette-Guéin (BCG) vaccine is the oldest vaccine that continues to be widely used nowadays. It is derived by in vitro attenuation of an isolate of Mycobacterium bovis specially cultured in an artificial medium for years and named after its discoverers, the French bacteriologist Albert Calmette and veterinarian Camille Guéin. The product was subsequently distributed to many laboratories, which continue to propagate the vaccine strain under different conditions. The marketed strains of BCG from different pharmaceutical companies are now bacteriologically different.1
BCG was first used in humans to prevent tuberculosis (TB) since 1921. It is now used worldwide in childhood immunisation programmes. It helps to protect vaccinees, especially infants and children, against disseminated TB and tuberculous meningitis, with an estimated efficacy of 78% and 64%, respectively.2 The efficacy for protection against pulmonary tuberculosis in adults and children remains unclear.3 However, BCG still is one of the most cost-effective vaccines, which only costs about HK$1,600 per life-year gained.4 In Hong Kong, the universal neonatal BCG immunisation programme was introduced since April 1952, which dovetailed a declining TB notification rate from 697.2 per 100,000 population in that year to 76.36 per 100,000 population (provisional figure) in the year 2009. Neonatal BCG vaccination coverage in Hong Kong has been persistently around 99% since 1980.5
Complications from BCG Vaccination
BCG vaccine is considered to be safe and has a low incidence of serious adverse reactions.6,7 The most common complications after receiving BCG are local reactions and regional lymphadenopathy.8-10 The local reactions at the inoculation site can range from erythema and induration, to the formation of papule, discharging ulcer or abscess. Regional lymphadenopathy arises as a result of enlargement of ipsilateral lymph nodes, principally involving the axillary, and rarely, the lower cervical chain. The higher the BCG injection site above the insertion of the tendon of the deltoid muscle, the higher the likelihood of cervical lymphadenopathy, if regional complication does occur. Serious complications such as regional or distant soft tissue granulomas, osteomyelitis and disseminated disease (disseminated BCGosis) are rare, which mainly affect patients with impaired immunity, like those with acquired immunodeficiency syndrome (AIDS) or primary immunodeficiencies.11-13 However, similar complications can rarely occur in previously healthy or immunocompetent individuals. Notwithstanding, further investigations for an underlying aetiology or immune defect is warranted whenever serious complications develop after BCG vaccination.
Regional lymph node enlargement after BCG vaccination generally undergoes spontaneous resolution but may occasionally progress slowly to become suppurative.13,14 This is a continuous spectrum of lymph node reactions and there is no specific guideline or recommendation to clearly define and differentiate normal from abnormal. The term "BCG lymphadenitis" is usually coined when ipsilateral axillary, supraclavicular or lower cervical lymph node enlargement developing after BCG vaccination is severe enough to arouse significant concern from the child care provider to seek medical attention.14
Types of BCG Lymphadenitis
There are two forms of BCG lymphadenitis.15,16 The non-suppurative form (simple form) is characterised by a benign clinical course and the lesion resolves spontaneously without any sequelae over a period of weeks17 (Figures 1a & 1b). The suppurative form is marked by the progressive enlargement of regional lymph nodes leading to a collection of suppurative material, with recognisable fluctuation in the swelling. Overlying skin changes is universal, with erythema, edema, increased pigmentation and pustule formation (Figures 2a & 2b). If left untreated, the suppuration will eventually rupture, leading to persistent caseous discharge and sinus formation (Figure 3). Wound healing inevitably takes several months, which is unpleasant to both patients and their care providers. Frequent and meticulous wound dressing is required, and secondary bacterial infection, unsightly scarring or keloid formation are not uncommon sequelae.18
Infants suffering from BCG lymphadenitis are commonly referred to the Hospital Authority Infectious Disease Centre of Hong Kong for further evaluation. We present an illustrative case series to describe the characteristics and outcome of infants affected by the condition who were managed in our centre over a 5-year period. This is followed by a review of the risk factors for development of the disease entity, clinical features and approach to its proper management.
Table 1 summarises our recent experience in the management of 11 infants who presented with suppurative BCG lymphadenitis from January 2006 to December 2010. Seven of them were male infants (male to female ratio of 1.75 to 1). All of them had received BCG vaccination (9 at birth, 1 at 2 months and 1 at 11 months of age) and presented with isolated left axillary mass which later suppurated as the only abnormal physical finding at a mean of 3.5 months (range 2 to 5 months) after vaccination. All were thriving well and none of them developed fever or constitutional symptoms. Tuberculin skin tests were performed in 7 of them using 2 units of tuberculin (PPD-RT23) administered by the Mantoux method. Six were positive (≥10 mm induration at 48 to 72 hours after intradermal injection) and the remaining one had an induration of 9 mm. None had abnormal findings on chest radiographs. Bacteriologic investigations were performed in 9 infants. Mycobacterium bovis (BCG strain) was isolated from culture of the needle aspirates obtained from the enlarged suppurative axillary lymph nodes of 5 infants. Three of 5 infants who had incision and drainage performed (Cases 1-4 prior to referral to our care and Case 5 after failed needle aspiration) were also culture-positive for BCG. Of the remaining 2 patients, 1 was culture-negative (Case 3) and the other (Case 4) was not subjected to microbiologic investigations by the referring doctor. One infant (Case 11) had spontaneous rupture with minimal discharge of the axillary lymph node 1 month after presentation.
Needle aspirations were attempted in 6 infants (Cases 5-10). One of them (Case 5) failed the attempt (dry tap) and subsequently underwent incision and drainage twice despite our referral for surgical excision. Wound healing took 3 months in this infant and was not satisfactory as he developed a 2 cm irregular scar. All 5 infants who were initially managed with successful needle aspiration alone showed significant regression in the sizes of their axillary lymph nodes after the procedure. Two infants with the lymph node sizes of 1-2 cm resolved completely over 2 to 4 weeks (Cases 6-7). However, enlargement of adjacent solitary lymph nodes occurred about 1 month after needle aspiration and spontaneous rupture ensued before the infants returned for follow-up. Despite this apparent failure of hastening recovery with needle aspiration, the discharge from the subsequently enlarging adjacent lymph nodes was minimal, requiring only simple dressing, and stopped spontaneously, one after 2 weeks and the other 4 weeks. The other 3 patients (Cases 8-10) had regression of lymph node size from 2.5 to 0.2 cm (92% reduction), 2 to 0.5 cm (75% reduction), and 1.5 to 0.4 cm (73% reduction) at 5, 6 and 3 months after needle aspiration, respectively, with no further complication or need for surgical intervention up to the time of latest follow-up (Figures 4a & 4b). In summary, five of the 6 infants who were managed initially with needle aspiration were spared surgical excision (Cases 6-10). The remaining one (Case 5) unfortunately was managed with a surgical procedure which was not our intention, resulting in suboptimal wound healing (Figure 5).
Surgical incision and drainage had already been performed in 4 other infants (Cases 1-4) prior to referral to our centre for further management of their persistently discharging wounds, and was also performed in the one referred for surgical excision after failed needle aspiration in our centre (Case 5). Daily wound toilet and dressing for an extended period in hospital, and then clinic until complete resolution were required. Unfortunately, upon healing all 5 of them developed significant irregular scarring and 2 eventually developed keloids over their scars, with 1 necessitating plastic surgical excision. The mean duration from incision and drainage to complete wound healing and resolution of the lymph node enlargement in these 5 infants who were managed by incision and drainage was 4 months (range 3 to 6 months).
The infant (Case 11) who had spontaneous rupture of the axillary lymph node that suppurated 1 month after presentation only required daily simple dressing. The draining sinus healed after 2 weeks and resolution of the lymphadenitis took 4 months to complete, leaving behind a 3 mm depressed scar. The resolution in this infant was fortunately satisfactory because the discharging content of the suppuration was not copious.
Isolated left supraclavicular lymphadenitis occurred in 1 infant (Case 2) 4 months after BCG vaccination, shortly after resolution of the axillary lymphadenitis. Unfortunately, incision and drainage was performed by surgeon and the wound took 4 more months to heal. Immune function tests performed in this patient were normal.
|Figure 6 Management algorithm for BCG lymphadenitis.|
Good immunisation technique, correct dosage and quality control of the BCG vaccine are presumed to be of paramount importance in avoiding untoward reactions following its administration. To prevent severe local BCG lymphadenitis and more extensive or disseminated BCG infection, avoidance of BCG vaccination in patients with known primary or acquired immunodeficiencies should be seriously considered. However, it is very difficult, if not impossible, to suspect or identify primary immunodeficiency at or soon after birth, unless there is a known family history or the patient presents with features of a known immunodeficiency syndrome (e.g. Di George syndrome). World Health Organization has made human immunodeficiency virus (HIV) infection in infants a contraindication to BCG vaccination in the revised consensus statement of 2008, though information on the risk-benefit ratio, especially in developing countries, is limited and the recommendation may be subject to further debate.13,38,39 We in Hong Kong have adopted the revised WHO recommendation of withholding BCG vaccination in infants known to be HIV positive as well as those born of HIV-infected mothers, pending testing for HIV infection.40
In summary, non-suppurative BCG lymphadenitis is a relatively common benign condition that will regress spontaneously over a matter of weeks to months. Reassurance and masterly inactivity with regular follow-up are all that is required. If the enlarged lymph node progresses to suppuration, then needle aspiration (which can be repeated if necessary) should be performed first in an attempt to hasten resolution by emptying its content, and provide material for appropriate microbiological investigations. Complete surgical excision should be considered for failed needle aspiration or recurrence of suppuration despite repeated aspirations. The addition of antimicrobial therapy is of no proven benefit. Incision and drainage is mentioned to be condemned.
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