BCG lymphadenitis: a potential complication of immune reconstitution following haematopoietic stem cell transplant.

An MHC class II deficient 2-year-old boy presented with fever and an enlarging left neck mass 100 days post allogeneic haematopoietic stem cell transplant (HSCT). Fever persisted despite treatment with broad-spectrum ß-lactam antibiotics. His BCG vaccination site at presentation was quiescent. Ultrasound showed enlarged cervical lymph nodes. An incisional biopsy of the large nodal mass yielded acid-fast bacilli, identified as Mycobacterium bovis by genome sequencing. Treatment with rifampicin, isoniazid and pyridoxine was started. The mass suppurated (figure 1), before healing concurrently with T-lymphocyte reconstitution at approximately day 130 post-HSCT.

The role of surgical management of BCG vaccine-induced regional suppurative lymphadenitis in children: a 7 years' experience from one medical center.

BACKGROUND: The management strategy of Bacille Calmette-Guérin (BCG) vaccine-induced regional suppurative lymphadenitis in children is still controversial and more clinical studies are needed. We therefore present a surgical case series to explore the role of surgical management for this dilemma. METHODS: From January 2013 to June 2020, data from 65 patients diagnosed with BCG vaccine-induced regional suppurative lymphadenitis were retrospectively reviewed. Clinical characteristics, ultrasonographic findings, surgical procedures, perioperative management, and outcome were analyzed. The association between postoperative seroma and symptom duration, skin involvement, and postoperative hospital stay were compared using Yates's corrected Chi-square test and Student's t-test for statistical analysis. The follow-up period ranged from three to six months. RESULTS: Of the 65 cases, the median age at presentation was 3.4 months. All patients were full-term with normal range of birth weight and received a BCG vaccination in the first 24 h of life. All patients underwent surgical excision of the abscess with the involved lymph node(s). Postoperative seroma formation was found in 20 patients and fine needle aspiration was needed. There was no significant association between postoperative seroma formation with symptom duration, skin involvement, and postoperative hospital stay. No oral anti-tubercular agents were given postoperatively. The mean length of postoperative hospital stay was 6.02 ± 1.62 days. Sixty-four cases (98.46%) received only one procedure and recovered. One patient required a second procedure due to postoperative sinus. CONCLUSIONS: The present study showed that surgical excision of the abscess with involved lymph node(s) is one of the choices for BCG vaccine-induced suppurative lymphadenitis, but special attention should be paid to controlling the surgical indications. Intraoperative meticulous manipulation and postoperative care are crucial to achieve a good outcome.

Hypophysitis and other autoimmune complications related to immune checkpoints inhibitors´ treatment: Spectrum of imaging appearances.

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations.

Role of needle aspiration and surgical excision in management of suppurative Bacillus Calmette Guerin lymphadenitis.

The aim was to determine the role of needle aspiration and surgical excision in the management of suppurative Bacillus Calmette Guerin (BCG) lymphadenitis. This prospective study was done in Rafha Central Hospital, over 1.5 years. Thirty two patients were enrolled after informed consent. Needle aspiration was done if size of lymphadenitis was up to 3cm. Surgical excision was done primarily for size more than 3cm or in cases of failed aspiration. Eighteen were males and 14 were females. Median age was 3.75 months (IQR 2-7). All were full term with normal birth weight and vaccinated in first 2 days of life. Predominantly single region of lymphadenitis was involved in 75% cases; with left axilla being mainly affected (56.3% cases). Needle aspiration was done in 18 cases and surgical excision was carried out in 14 cases. Resolution of lymphadenopathy was 7 days in cases of surgical excision, while within 60 days in cases of aspiration. Failure of aspiration was noted in cases of multiple, matted suppurative lymph nodes.

SUSPECTED HYPOVITAMINOSIS A-ASSOCIATED SALT GLAND ADENITIS IN NORTHERN ROCKHOPPER PENGUINS ( EUDYPTES MOSELEYI).

Supraorbital salt-excreting glands are present in at least 10 avian orders and are largest in marine species, including penguins. Diseases of the avian salt gland have been described infrequently. From September 2015, five captive northern rockhopper penguins ( Eudyptes moseleyi) were presented over a 6-wk period for unilateral or bilateral supraorbital swellings. In September 2016, two cases recurred and two additional cases were identified. Histopathology demonstrated salt gland adenitis with extensive squamous metaplasia. Blood plasma testing demonstrated marked vitamin A and E deficiencies within the colony. Prolonged frozen storage of feed-fish was implicated as a cause of vitamin depletion; reducing storage times and addition of dietary supplementation prevented recurrence.

BCG vaccination-induced suppurative lymphadenitis: four signs to pay attention to.

Suppurative lymphadenitis is one of the severe complication after BCG vaccination, but its diagnostic criteria and treatment guidelines have not yet been established. In this article, we describe a case of suppurative lymphadenitis caused by BCG vaccination and propose diagnostic criteria and treatment guidelines of the disease. The lymphadenitis was presented as skin involving mass and was completely extirpated. Pathological evaluation revealed a necrotising lymphadenitis, consistent with the diagnosis of BCG lymphadenitis. The patient was administered adjuvant medical treatment with anti-TB medications (Isoniazid and Rifampicin) for 3 months. At 6 months follow-up, the disease was in complete remission without complications. We recommend focus on the following four signs when diagnosing BCG lymphadenitis: (i) previous history of vaccination on the ipsilateral side of the lesion, (ii) absence of any other infection signs, (iii) absence of fever and (iv) isolated axillary or supraclavicular/cervical lymph node enlargement proven by ultrasonography or computed tomography scan. BCG vaccination-induced suppurative lymphadenitis can easily be overlooked, but prompt, accurate diagnosis followed by appropriate surgical resection should result in complete healing as in this case.

Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons.

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

[The role of immunodeficiencies in development of complications during vaccination of children with BCG vaccine].

AIM: Study of the interrelation between the presence of immune deficiency and development of complications during vaccination of newborns with BCG vaccine. MATERIALS AND METHODS: In 24 children with complications of vaccine process in the form of cold abscess and lymphadenitis indicators of lymphocyte subpopulation levels were studied by flow cytofluorimetry on Beckman Coulter cytofluoriemter by using monoclonal antibodies with markers CD45+CD3+ - T-cell, CD45+CD3+CD4+ - T-helpers, CD45+CD3+CD8+ - T-supressors-cytotoxic killers, CD45+CD3 CD16+CD56+ - natural killers, CD45+CD3-CD19+ - B-lymphocytes. The level of IgG, IgA, IgM in sera was determined by immune diffusion method in agar by Mancini. RESULTS: In 4 children selective deficiency of IgA, in 5 - hyper-IgM syndrome was detected, which is an innate immunodeficiency and is characterized by the lack of sera IgA, reduction of IgG level and increase of IgM. In 9 children a reduction of CD16+ natural killer lymphocytes was detected, in some cases combined with a reduction of CD8+ T-supressors-cytotoxic killers. CONCLUSION: The reason of development of complications during BCG administration is the presence of immunodeficiency in children. In these children severe course of the vaccine process, presence of axillary lymphadenitis was observed, therapy of these children continued from 4 to 6 months.

Multiple high-grade and rare immune-related adverse events in a colon cancer patient with genomic and cytokine profiling.

We report a case of multiple high-grade and rare immune-related adverse events (irAEs) in a patient with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A middle-aged MSI-H mCRC patient with metastases to the lungs and lymph nodes received several lines of chemotherapy and immunotherapy and developed five different high-grade irAEs during immunotherapy, including lymphadenitis, pneumonitis, hypophysitis, thyroiditis and transverse myelitis. Genomic profiling revealed high tumor mutational burden of 43 Muts/Mb. Cytokine profiling showed a threefold increase in MMP-9 shortly prior to the onset of lymphadenitis and a fourfold increase of Ang-1 1 week after the resolution of lymphadenitis. Further studies are warranted to investigate the association of MSI-H mCRC with irAEs and the role of cytokines in predicting irAEs.

Immune-related adverse events (irAEs) are a potential side effect of taking immunotherapy treatment for cancer. We report a case of a patient with a highly mutated form of metastatic colon cancer who developed five unique and severe irAEs while receiving immunotherapy. The patient developed inflammation of the lymph nodes, lungs, pituitary gland, thyroid and spinal cord. Genetic testing showed that the tumor was highly mutated (43 Muts/Mb). Analysis of cell signaling proteins called cytokines revealed that MMP-9 sharply increased before the onset of lymphadenitis and Ang-1 sharply increased after its resolution. Further research is needed to understand the relationship between highly mutated colon cancer and irAEs as well as the role of cytokines in predicting the onset and resolution of irAEs.

Epidemiological characteristics and trends of Bacillus Calmette-Guérin lymphadenitis in Shanghai, China from 2010 to 2019.

Although the administration of the Bacillus Calmette-Guérin (BCG) vaccine is generally safe, lymphadenitis, the most common complication of BCG vaccination, can occur. Here, we describe the epidemiological characteristics and incidence trends of BCG lymphadenitis in Shanghai, China, among a population with a high burden of tuberculosis. A total of 56 cases of adverse events following immunization (AEFI) after BCG vaccination were reported in Shanghai, including 51 cases of BCG lymphadenitis (91.07%), from 2010 to 2019. The general incidence of BCG lymphadenitis was 173 per 1,000,000 doses in Shanghai from 2010 to 2019. A nonsignificant increase of 58.81% per year was observed between 2010 and 2012 (t = 0.93; p = .40), followed by a significant decline of 28.00% per year from 2012 to 2019 (t = -4.27; p < .01). Seven batches of BCG vaccines triggered three or more BCG lymphadenitis cases, for 27 (52.94%) cases in total. We identified two patients with immunodeficiency of chronic granulomatous disease, one of whom died four years later after BCG vaccination and another of whom was still being treated after two transplants. The average total care cost of the 47 recovered cases was 11,336 RMB (range: 2,637-33,861 RMB). Due to the high burden of BCG lymphadenitis, especially in children with immunodeficiency, it is suggested that government departments should strengthen healthcare provider training, assign specific nurses to perform BCG vaccination, monitor vaccinated individuals actively and timely detect abnormal signals so as to reduce the incidence of BCG lymphadenitis.

New mimic of relapse or regional lymph node metastasis in a cancer survivor: a case of mRNA COVID-19 vaccine-induced lymphadenitis with high FDG uptake.

Western countries that were first to administer the COVID-19 vaccination report cases of vaccine-induced axillary lymphadenitis with high FDG uptake. However, no such findings have been reported from any Asian countries. We report here a confusing case of a 31-year-old female cancer survivor with high FDG uptake in her axillary lymph nodes, suggesting recurrence, following mRNA COVID-19 vaccination. Although the value of SUVmax was elevated (12.7), additional imaging revealed that her lymphatic lesions were benign, and they resolved spontaneously. This case of a strong immune reaction to COVID-19 vaccination in regional lymph nodes is the first reported in a Japanese patient. We should be aware of this new mimic and optimize diagnostic imaging methods accordingly in the era of COVID-19.

Interferon-gamma +874 T/A and interleukin-10 -1082 A/G single nucleotide polymorphism in Egyptian children with tuberculosis.

The aim was to investigate the association of interferon-gamma (IFN-γ) +874 T/A and interleukin-10 (IL-10)-1082 A/G single nucleotide polymorphisms with tuberculous infection and post-BCG lymphadenitis in Egyptian children. IFN-γ +874 T/A and IL-10 -1082 A/G polymorphism detection by amplification refractory mutation system technique was carried out for 110 patients with TB, 40 patients with post-BCG lymphadenitis and 118 healthy controls. IFN-γ +874 A allele was higher in TB and post-BCG patients than those in healthy controls (Pc=0.006 and 0.002, respectively). IFN-γ +874 genotype AA was significantly higher in patients with TB than that in control (Pc=0.015), in extrapulmonary than patients with pulmonary TB (PTB) (Pc=0.009), and young children with TB below 5 years (Pc=0.024). No statistically significant differences were observed between patients with TB and controls for the frequency of IL-10(-1082) alleles or genotypes (P>0.05); however, a statistically significant difference in the frequency of IL-10 (-1082) GG genotype was found between patients with pulmonary and extrapulmonary TB (Pc=0.003). Low producer IFN-γ +874 A/A genotype is associated with post-BCG lymphadenitis and TB disease especially in younger children below 5 years. IL-10-1082 G/G genotype did not exhibit significant association except for increased GG frequency in PTB. Both cytokine polymorphisms have no relation to tuberculin reaction in patients with TB.

Surveillance of adverse events following immunization: 10 years' experience in Oman.

A descriptive record-based review of adverse events following immunization (AEFI) was carried out in Oman using the national database for the period 1996-2005. A total of 790 adverse event reports were received with an annual rate during the review period of 33.7 per 100 000 population or 10.8 per 100 000 doses administered. There were no reported deaths. The most frequently reported AEFI were BCG adenitis (69.7 per 100 000 doses) and local reactions (3.6 per 100 000 doses respectively). The statistically significant higher rates among males, in children aged > 2 years and in some sparsely populated regions of Oman need further research. AEFI rates in Oman were similar or below the international averages

Bacille Calmette-Guérin lymphadenitis and immune reconstitution syndrome in HIV-infected children on antiretroviral therapy in Jamaica.

The immune reconstitution inflammatory syndrome (IRIS) is a recognized complication associated with opportunistic infections occurring in HIV-infected individuals after the initiation of highly active antiretroviral therapy (HAART). We report on three HIV-infected infants with rapid progressor HIV disease who present with IRIS due to the BCG vaccine and occurring 3-6 weeks after initiation of HAART

Case Report of Ipilimumab-Induced Diffuse, Nonnecrotizing Granulomatous Lymphadenitis and Granulomatous Vasculitis.

Ipilimumab is indicated for the treatment of melanoma in both the metastatic and adjuvant setting. Ipilimumab inhibits cytotoxic T-lymphocyte antigen 4, leading to the augmentation of T-cell activity and an antitumor immune system response. The side effect profile of ipilimumab consists of autoimmune-like events such as dermatitis, colitis, and thyroiditis. These immune-related adverse events can be serious, often resulting in the need for systemic immunosuppression with corticosteroids. We present a case of diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis in a heavily pretreated patient with metastatic melanoma. After completion of 4 cycles of ipilimumab for the treatment of metastatic melanoma, our patient complained of increasing fatigue, drenching night sweats, and chills. Imaging revealed diffuse adenopathy involving several lymph nodes. Biopsy was positive for nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis. High-dose prednisone was initiated and tapered gradually over 6 weeks, resulting in complete resolution of the granulomatous disease.