• 
• 

Three Part Question

In [infants, less than 3 years, with suppurative BCG lymphadenitis], is [surgical intervention superior to medical or conservative management] in [terms of resolution]?

Clinical Scenario

A 3 month old term male infant of Somali background presented with a history of recurrent left axillary abscess, 1.5 cm in diameter, following BCG vaccination at birth. Swelling of the left axillae was noted at age 1 month along with keloid scarring of the injection site and this was diagnosed as BCG lymphadenitis at 2 months of age, supported by ultrasound scanning. The patient remained afebrile and otherwise fit and well, and there was no family history of Tuberculosis (TB) infection or recent travel and both parents had received the BCG immunisation. At 3 months of age the patient was admitted via the emergency department due to worsening of symptoms; this resulted in incision and drainage of the abscess alongside a short course of oral Co-Amoxiclav. Histopathology showed acid fast bacilli, though swab cultures were negative on Ziehl Nielson staining. A fortnight later the patient re-presented with increased exudate and erythema of the surgical site, alongside presumed viral gastroenteritis. He received a further short course of intravenous Co-Amoxiclav and was discharged with advice on conservative management.

Search Strategy

Databases searched using NHS Evidence: Medline, EMBASE, AMED, HMIC, BNI.


Search Terms:
“BCG vaccine” AND “lymphadenitis”
“BCG vaccine” AND “suppurative lymphadenitis”
“BCG vaccine” AND “adverse reactions”
“BCG vaccine” AND “abscess”
“BCG vaccine” AND “Erythromycin”
“BCG vaccine” AND “Isoniazid”
“Infant OR bab OR paediatric OR pediatric” AND “BCG OR Bacille Calmette-Guerin” AND “medical OR surg”

Search Outcome

104 Unique results, 8 directly related to the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chan WM et al 2011	11 infants aged 2-13 months who presented with suppurative BCG lymphadenitis having previously received the BCG vaccination. All had an isolated left axillary mass which later suppurated. All were otherwise well.	Case series	Wound outcome at follow up – time to heal, whether there was complete resolution and time taken, and any resulting scar formation including keloid.	5 infants underwent incision and drainage, all had resulting scarring and healing took 3-6 months. 5 infants underwent needle aspiration, two has complete resolution of the lymphadenitis, the others were continuing to resolve at follow up. Complete resolution in <1 month. Spontaneous rupture in one infant, resolved in 4 months.	Small numbers. Not randomised – in four patients the incision and drainage occurred prior to referral, the other took place after failed aspiration. Not blinded. No control group.
Abuzeid AF et al 2011	89 infants, the majority with unilateral axillary lymph node enlargement with symptoms starting 2 months after vaccination.	Case series	Recovery.	All but one infant had complete recovery by end of study period. (47% = conservative, 30% anti-TB, surgery 11.5%). The study suggests any method is suitable for the treatment of lymphadenitis.	Descriptive study, not randomised. Included those with disseminated tuberculosis.
Nazir Z et al 2005	60 otherwise healthy children aged 2 months to 6 years. All received BCG in first 2 months of life.	Case series	Cure rate (not defined), wound infection ,seroma and disease progression.	Surgical intervention resulted in 100% resolution but 2 infections and 3 seroma. 3/8 with medical treatment only progressed. Medical treatment is not effective when node size is >3cm or there is fluctuation or erythema of overlying skin. Advocate surgical excision.	Those with larger nodes >3cm underwent surgery, those with smaller nodes/no erythema had medical treatment. Not randomised. Also no comments on type of surgical intervention. No comments on outcome – i.e. scarring. No control group. All patients were receiving medical treatment on referral. Surgical patients also received medication post op. The late presentation of some patients (up to 5years) raises the question of whether this was BCG related.
Sataynarayana S et al 2002	18 infants	Case review	Resolution	All cases were treated with weekly aspiration resulting in a mean period of resolution of 8 weeks. Anti-tubercular treatment is not required.	Another study performed after a change in vaccine resulted in an outbreak of lymphadenitis. Small study size and no control group to compare results with.
Hengster P et al 1997	116 infants given BCG vaccine as newborns. Otherwise medically fit.	Case series	The outcomes were not made clear – healing rate?	Isoniazid therapy did not prove successful when inflamed lymph nodes exceeded a certain size. Suppurative lymphadenitis in lymph nodes exceeding 1.0 to 1.5 cm usually led to infiltration or even perforation of the skin. Surgery prevents these complications and significantly reduces healing time; wound healing was significantly shorted compared to other groups (conservative and Isoniazid therapy) for example 28 weeks in the conservative group compared to 4 weeks in the surgical group. Adjuvant isoniazid therapy cannot be recommended, except for generalized BCG tuberculosis.	No table of results so couldn’t interpret data. No control group and not randomised; those treated surgically had fluctuant nodes >1.5cm or nodes that had spontaneously discharged. Statements were not backed by statistics. One of the larger studies but it is not clear how it was conducted. The vaccine given (Pasteur intradermal, P, R5520) caused an outbreak and is now prohibited.
Merry C et al 1996	17 patients, 16 of who received vaccination in newborn period. All otherwise fit and well.	Case series	Resolution or disease progression	All but one of the medically treated patients and both observed patients required surgery for failure to resolve/progression. Best results from excision and primary closure.	Small number of cases, not randomised, no control. As with a previous study the patient group had received a strain of vaccine that had resulted in an outbreak of lymphadenitis – Copenhagen 1331.
Banani SA et al 1994	77 Infants and children with confirmed abscess, not immunocompromised. 43 in study group 34 in control. Ages 1-36 months, majority vaccinated in first 2 weeks of life.	RCT not blinded.	Regression. Spontaneous sinus tract formation and drainage. Node size over time.	Regression rate in the study group two, four, and six months after needle aspiration was significantly higher compared with the control group (58% at 2 months vs 9% and then 95% at 6 months vs65%). No recurrence were observed up to six months after healing. Spontaneous drainage with development of sinus tract formation was also markedly less in the study group compared with the control group six months after needle aspiration (7% vs 44%).	Good exclusion criteria: previous medical treatment, immunocompromised, generalised adenopathy. Randomly assigned. Not blinded. Some patients required repeat aspiration.
Caglayan et al 1991	50 children with suppurative regional BCG lymphadenitis	Case review	Need for further surgery/recovery	23 patients in aspiration group and 27 in the drainage group (11 incisional and 16 spontaneous). Of these 10 in the drainage and 3 in the aspiration group required total excision. The other 20 in aspiration group recovered. Drainage took on average 7.5 weeks to heal. Simple needle aspiration is sufficient for the treatment of suppurating but non-drained BCG lymphadenitis. For suppurating lymph nodes that were surgically (not recommended) or spontaneously drained, a more invasive procedure, total surgical excision, is proposed.	No control group (i.e. no intervention). Does not assess scarring/wound outcome. A high number in the drainage group underwent spontaneous drainage which is associated with poorer outcome in other studies.

Comment(s)

The Bacille Calmette-Guerin (BCG) immunization programme in the UK was introduced in 1953 and, having undergone a number of changes since, is currently risk based and largely dependent on neonatal vaccination. Those born in areas of the UK with an annual incidence of tuberculosis greater than 40/100,000, born to parents/with grandparents from a country of high incidence, birth or living for an extended period in a high risk country, or contact with a person with confirmed tuberculosis should be vaccinated (Goraya, 2002). Occupational vaccination also exists. The vaccination efficacy is controversial though proposed to be approximately 70-80%, with greater benefit for the more serious conditions of tuberculosis meningitis and disseminated tuberculosis (Green Book Anon, 2011). Estimated efficacy rates for disseminated TB and tuberculous meningitis, are quoted as 78% and 64%, respectively (Chan, 2011). The BCG is a live attenuated vaccine of Mycobacterium Bovis; there is therefore a potential risk of infectious sequelae. Complications include lymphadenitis, allergic reaction and disseminated disease; additionally 95% of patients experience mild symptoms such as site reactions and minor lymphadenopathy (Green Book Anon, 2011). BCG lymphadenitis is a common complication; it is divided into simple and suppurative, with the simple form being more common. Lymphadenitis typically occurs 2 weeks to 6 months post immunisation and tends to affect the axillary nodes (95%), however the supraclavicular and cervical nodes can be affected (Goraya, 2002). Risk factors for lymphadenitis can be divided into vaccine, host and delivery related. Increased virulence, viability and dose of the vaccine have been linked to increased incidence of lymphadenitis; a number of outbreaks have occurred linked to introduction of a new-higher virulence-strain. Newborns are particularly at risk of lymphadenitis, with double the risk, as are those who are immunocompromised or already tuberculin positive (Banani, 1994; Goraya 2002) This is why a repeat BCG is not recommended – the risks outweigh the benefits (Green Book Anon, 2011). Finally poor injection technique is associated with greater occurrence of lymphadenitis (Chan, 2011; Goraya, 2002). Regional lymph node enlargement after vaccination tends to undergo spontaneous resolution, however may progress to become suppurative (Chan, 2011). Simple lymphadenitis can be managed conservatively, however the managed of the suppurative form is controversial. Over time spontaneous perforation and sinus formation is almost universal amongst those with suppurative lymphadenitis. This report has aimed to summarise the evidence of the management of BCG related suppurative lymphadenitis. Many techniques have been tried, with four main options including: conservative management, medical management with antibiotics or anti-tuberculous medications, needle aspiration and finally surgical management including incision and drainage or excision. Medical management has largely been discounted as non beneficial and in randomized control trials it has not been found to prevent suppuration or shorten healing time (Goraya, 2001). In general needle aspiration seems to be favored first line, however there are those who recommend surgical excision, particularly for large, multiloculated or matted nodes (Green Book Anon, 2011; Hengster, 1997; Merry, 1996; Nazir, 2005 ). Needle aspiration appears to prevent spontaneous perforation, reduces healing time and results in better cosmetic appearance; it is also a safer option, not requiring general anaesthetic (Banani 1994; Caglayan 1991; Chan 2011; Sataynarayana 2002) . Simple incision and drainage is not recommended because it results in persistent discharge requiring cumbersome dressing, inadequate evacuation of inflammatory materials, suboptimal wound healing, scarring and delayed recovery (Chan 2011; Goraya 2002). Surgery should be reserved for those with repeated collections after needle aspiration, especially if the nodes are matted and multilocular (Banani 1994).

Clinical Bottom Line

Management of BCG lymphadenitis remains controversial and the studies undertaken thus far do not provide a satisfactory level of evidence to make definite decisions. General consensus is that needle aspiration should be used first line in suppurative lymphadenitis, as this results in quicker resolution and reduced scarring. Should this fail surgical excision may be attempted. The evidence for medical therapy is very poor and is therefore not recommended.

References

1. Chan WM, Kwan YW, Leung CW. Management of Bacille Calmette-Guerin lymphadenitis. Hong Kong Joural of Paediatrics 2011;16(2):85-94
2. Abuzeid AF, Dahabreh MM, Habashneh MS, Obeidat AN, Abuhammour W. Bacille Calmette-Guerin lymphadenitis: a single centre experience. Journal of paediatric infectious disease 2011;6(1):37-40
3. Nazir Z, Qazi SH. Bacille Calmette-Guerin (BCG) lymphadenitis-changing trends and management. Journal of Ayub Medical College 2005;17(4):16-18
4. Sataynarayana S, Mathur AD, Verma Y, Pradhan S, Bhandari MK. Needle aspiration as a diagnostic tool and therapeutic modality in suppurative lymphadenitis following Bacillus Calmette Guerin vaccination. Journal of the Association of Physicians of India. 2002;50:788-91.
5. Hengster P, Solder B, Fille M, Menardi G. Surgical treatment of Bacille Calmette-Guerin lymphadenitis. World Journal of Surgery 1997;21:520-523
6. Merry C, Fitzgerald RJ. Regional lymphadenitis following BCG vaccination. Paediatric Surgery International 1996;11(4):269-271
7. Banani SA, Alborzi A. Needle aspiration for suppurative post-BCG Adenitis. Archives of Disease in Childhood 1994;71:446-447.
8. Caglayan S, Arikan A, Yaprak I, Aksoz K, Kansoy S Management of Suppuration in Regional Lymph Nodes Secondary to BCG Vaccination. Pediatrics International 1991;33(6):699-702.