BCG is a live attenuated vaccine which is extensively used worldwide[2, 18]. BCG-associated adverse events include injection site abscess and ulceration, BCG vaccine-related lymphadenitis, osteomyelitis and disseminated BCG diseases[2, 19], which were classified into five categories, i.e., adverse event (AE), adverse reaction (AR), severe adverse event (SAE), severe adverse reaction (SAR), and suspected unexpected severed adverse reaction (SUSAR)[20]. BCG vaccine-related lymphadenitis, defined as the development of ipsilateral regional enlarged lymph nodes following BCG vaccination, is considered to be one of the most common complications[8, 18]. Regional and suppurative lymphadenitis were classified as AR and if leading to hospitalization, they were classified as SAE[20].
The occurrence of BCG vaccine-related lymphadenitis is mainly due to improper vaccination, such as the vaccinators' skills and experience, subcutaneous injection, excessive dose of BCG and residual virulence of BCG strain, immunocompromised individuals, younger age, etc[5,21−23].
In Sadeghi-Shanbestari study, except for 2 cases who were under 3 years old, the rest were male and they were less than one year old, and 48 infants with BCG lymphadenitis, within range of 2–62 months (9.9 ± 9.85) were selected[24]. In our study, except 5 cases that were within 4.4 years old, all of them were younger than one year old, and 65 infants with BCG lymphadenitis, within range of 1–52 months (5.83 ± 8.17) were selected. The results were similar.
BCG vaccine-related lymphadenitis is classified into two forms: suppurative and non-suppurative. Approximately 60% of non-suppurative lymphadenitis develops into suppurative lymphadenitis, the affected lymph nodes show swelling and redness of the overlying skin, abscess formation (with fluctuation), and eventually rupture and a sinus tract is formed[12, 19, 21]. In our study, BCG vaccine-related lymphadenitis frequently involved the left axillary lymph node, followed by the supraclavicular lymph node, and left cervical lymph node. Occasionally, lesions were observed in the left axillary and supraclavicular lymph nodes or left axillary and left subscapular latissimus dorsi lymph nodes. Similar results were reported by Bukhari[12]. As the injection site for the vaccine is usually located on the left arm, BCG-related lymphadenitis occurred in the ipsilateral axillary, and even in the neck or back. Some experts have reported that right axillary lymphadenitis occurs when the injection site is on the right arm[25].
Although several methods for the management of regional lymphadenitis with abscess formation have been reported[1, 3, 7, 21], each method has advantages and disadvantages. Nowadays, the reported methods include clinical observation, oral antituberculosis drugs, needle aspiration, incision and drainage, and surgical excision of lymph nodes. Non-suppurative lymphadenitis (< 1 cm) is suitable for observation and in some cases may resolve spontaneously[5]. Some authors have reported that oral erythromycin or anti-tuberculosis drugs such as isoniazid (alone or in combination with rifampin) for BCG vaccine-related lymphadenitis treatment had no significant effects on both suppurative lymphadenitis and ulceration. The use of anti-tuberculosis drugs in infants may lead to a high incidence of adverse effects[7].
Needle aspiration with or without instillation of isoniazid or rifampicin can decrease the occurrence of spontaneous rupture but does not debride the lesions[5, 21, 26, 27]. Surgical management of BCG vaccine-related lymphadenitis has been reported to have fewer side effects and shorter treatment time[10, 13, 17, 28]. In the present study, 65 children with BCG vaccine-related lymphadenitis underwent excision of the lesions en bloc, and most patients recovered uneventfully.
Postoperative seroma formation occurred in 20 patients (20/65, 30.77%), the effusion was aspirated using a fine needle and the wound was bandaged with appropriate pressure after aspiration. The seroma disappeared after two to five aspirations. Only one child required re-operation due to abscess recurrence. The average length of hospital stay in our study was 9.32 ± 2.34 days (range: 4–17 days). Nazir et al[29] found that of all the patients who received anti-tuberculosis drug treatment for one to nine months, fifty-two children who presented with large fluctuant lymph nodes required a surgical procedure. However, surgical management can shorten the duration of healing.
Although our study shows that surgical treatment of BCG vaccine-related lymphadenitis has many advantages, we should also follow its natural course and be cautious in choosing surgical treatment. In our experience, surgeons should pay more attention to the following steps. (1) large abscesses should be aspirated before excision to avoid rupture and contamination of the wound; (2) the extent of the deep tissues to be excised should be limited to the involved parts in order to protect the axillary vessels, nerves and normal lymph nodes. In some cases, lesions may tightly adhere to the axillary sheath, and electrocautery should not be used as underlying axillary vessels and nerves may be damaged; (3) before suturing the incision, fluid and air should be removed and the wound bandaged with appropriate pressure to decrease the risk of seroma formation.