The spectrum of cytological findings in patients with BCG lymphadenitis: A series of 13 cases.

CONTEXT: Bacillus Calmette-Guérin (BCG) vaccine has been used to prevent tuberculosis and/or its severe complications for long. BCG lymphadenitis is a common complication of the vaccine, which is sometimes subjected to cytological examination. The aim of the study is to describe the cytological findings of BCG lymphadenitis. SETTINGS: The study was conducted in a tertiary care hospital in the western part of India from January 2021 to December 2022. DESIGN: The study was performed on archived material of all patients who were referred to the fine needle aspiration clinic for cytology examination. Clinical and pathological data of cases were retrieved, and cases of BCG lymphadenitis were selected in the study based on these data. Slides of cases were retrieved, and cytological findings were studied. MATERIALS AND METHODS: Papanicolaou, Giemsa, and Hematoxylin & eosin-stained smears, as well as Ziehl-Neelson stain (Z.N. stain) smears of all BCG lymphadenitis cases, were retrieved. Cases were reviewed for individual cytological features and overall cytological diagnostic categories. Z.N. stain smears were evaluated for acid-fast bacilli. RESULTS AND CONCLUSIONS: Diagnostic categories observed in BCG lymphadenitis include suppurative lymphadenitis/abscess (15 %), necrotizing lymphadenitis (23 %), necrotizing granulomatous lymphadenitis (46 %), suppurative granulomatous lymphadenitis (8 %), non-necrotizing granulomatous lymphadenitis (8 %). Acid-fast bacilli were detected by Z.N. stain in 8 cases (62 %). The cytological findings of BCG lymphadenitis closely overlap with those of tuberculous lymphadenitis. So, clinical context is very important while reporting isolated axillary lymphadenopathy, specifically in recently vaccinated infants, to avoid misdiagnosis as tuberculous lymphadenitis.

Clinical, Microbiological Profile and Treatment Outcomes of Infants with BCG Adenitis: A Retrospective Study.

BACKGROUND: Bacille Calmette-Guérin (BCG) adenitis is an uncommon complication following BCG vaccination. In rare cases, infants can develop other complications. Controversy exists regarding the diagnosis and management of these cases. Not much information is available in literature regarding their microbiological and immunological characteristics. METHODS: Electronic medical records of children presenting to the Pediatric Infectious Diseases clinic in a tertiary care hospital from January 2011-December 2020 with a diagnosis of BCG adenitis were retrospectively reviewed. Their clinical, microbiological, treatment and follow-up data were noted and analyzed. FINDINGS: During the study period, 40 infants presented with a probable diagnosis of BCG adenitis with or without disseminated BCG. Median age at symptom onset was 4(2.5-5.9) months. Nine infants had disseminated disease at presentation. Fifteen infants were suspected to have underlying immune deficiency of whom 12 had proven defects in immune function. On multivariable logistic regression analysis, presence of disseminated disease was the only factor predictive of underlying immunodeficiency. Isoniazid monoresistance was seen in seven cases (32%) of the 22 samples sent for TB cultures. CONCLUSIONS: Though BCG adenitis runs a benign course, it could rarely be the first manifestation of an underlying immune defect. There is sizable isoniazid monoresistance, hence sending tissue samples for microbiologic evaluation is necessary to guide anti-tubercular therapy.

IL-1ß blockade in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: case-based review.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are considered as inflammasome disorders associated with uncontrolled interleukin (IL)-1ß production. Anti-IL1 agents are used in colchicine-resistant cases of FMF. Increase in pro-inflammatory mediators even between febrile attacks in PFAPA suggests that anti-IL1 treatment might be beneficial in these patients. We describe a child presenting with recurrent, self-limited febrile attacks at 1 year of age who was diagnosed as FMF being heterozygous for M694 V mutation. Her clinical findings were only controlled by the addition of canakinumab (2 mg/kg/8 week) to colchicine treatment. However, she developed typical PFAPA attacks during this treatment at 3 years of age. We conducted a literature search focusing on English articles with keywords including PFAPA, anakinra, canakinumab, and rilonacept. Five children and one adult patient with PFAPA were found and evaluated. Anakinra was reported to abort PFAPA attacks in children, while the adult patient first responded and then became resistant to anakinra. Canakinumab was effective in preventing febrile attacks in this patient. Failure of canakinumab to prevent PFAPA attacks in our case may arise from the differences in the pathophysiology of PFAPA and FMF. Thus, further experience with higher doses or shorter intervals of canakinumab is needed in children with PFAPA.

Vestibular involvement of PFAPA syndrome.

OBJECTIVE: PFAPA syndrome is derived from the initials of the English words of the findings that make up the syndrome ("Periodic Fever", "Aphthous Stomatitis", "Pharyngitis", "Adenitis"). This study aims to evaluate the vestibular system in patients with PFAPA syndrome by the cVEMP test and to give a general review of PFAPA syndrome in light of current literature. METHODS: In this prospective study, 30 patients aged 4-6 who were diagnosed with PFAPA in a tertiary pediatrics clinic, between January 2016 and February 2020 and 30 children of the same age group who applied to a tertiary otorhinolaryngology clinic for other reasons and proven to have no hearing or vestibular problems were included and in addition to routine physical examination, electromyographic activity of the sternocleidomastoid muscle surface was measured. RESULTS: We found that the amplitude difference between cVEMP p1-n1 in patients with PFAPA syndrome in both ears decreased compared to the healthy control group. CONCLUSION: Our study proves there is a vestibular system involvement of PFAPA syndrome. This study is the first in the literature to search the relationship between PFAPA and the vestibular system.

POPS case: A 30-year-old Filipino woman with fevers, lymphadenopathy, painful scalp lesions, and a neck mass.

We described a case of a 30-year-old Filipino woman who presented with fevers, night sweats, left hip pain, painful scalp lesions, and a neck mass. Symptoms began 6 months earlier, with nasal drainage, fever, cough, and occasional hemoptysis, which did not resolve with outpatient antibiotics. A further workup revealed lymphadenopathy and several lytic bone lesions. Her hospital course was later further complicated by the development of a tracheoesophageal fistula secondary to an esophageal mass and, then later, aseptic meningitis. Extensive diagnostic workup and immunologic tests were performed and finally led to the diagnosis. Here, we discussed the diagnostic workup and pathophysiology of the underlying condition. This case illustrated the importance of appropriate immunologic workup to make the diagnosis of a rare condition that proves to be clinically significant and presents challenges in management.

Cluster of Lymphadenitis due to Nontuberculous Mycobacterium in Children and Adolescents 8-15 Years of Age.

BACKGROUND: Nontuberculous mycobacteria (NTM) lymphadenitis is an under-recognized entity, and data of the true burden in children are limited. Without a high index of suspicion, diagnosis may be delayed and microbiological detection is challenging. Here, we report a cluster of NTM lymphadenitis experienced in Korean children. METHODS: Subjects under 19 years of age diagnosed with NTM lymphadenitis during November 2016-April 2017 and April 2018 were included. Electronic medical records were reviewed for clinical, laboratory and pathological findings. Information regarding underlying health conditions and environmental exposure factors was obtained through interview and questionnaires. RESULTS: A total of ten subjects were diagnosed during 18 months. All subjects were 8-15 years of age, previously healthy, male and had unilateral, nontender, cervicofacial lymphadenitis for more than 3 weeks with no significant systemic symptoms and no response to empirical antibiotics. Lymph nodes involved were submandibular (n = 8), preauricular (n = 6) and submental (n = 1). Five patients had two infected nodes and violaceous discoloration was seen in seven subjects. Biopsy specimens revealed chronic granulomatous inflammation and acid-fast bacteria culture identified Mycobacterium haemophilum in two cases and NTM polymerase chain reaction was positive in two cases. Survey revealed various common exposure sources. CONCLUSION: NTM lymphadenitis is rare but increasing in detection and it may occur in children and adolescents. Diagnosis requires high index of suspicion and communication between clinicians and the laboratory is essential for identification of NTM.

Risk factors for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study.

The etiology and pathogenesis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome are unclear. We performed a case-control study to evaluate potential environmental or lifestyle factors associated with PFAPA morbidity. We enrolled 119 patients with PFAPA syndrome who had undergone tonsillectomy in Oulu University Hospital between 1987 and 2007. We recruited 230 controls, matched for sex, birth date, and place from the database of the Population Register Center of Finland. All the patients and controls completed a questionnaire regarding exposure to environmental triggers during early childhood. Maternal smoking was more common among PFAPA syndrome patients than controls (23 vs. 14%; P = 0.005). PFAPA patients had lower breastfeeding rates than controls (94 vs. 99%; P = 0.006). No other environmental factors were associated with PFAPA syndrome, except having an aquarium at home (P = 0.007). The patient group also used natural or herbal medicines more often than the controls (P = 0.01). CONCLUSION: Maternal smoking and lack of breastfeeding, known risk factors for common childhood infections, were more common in patients with PFAPA syndrome than in matched controls. Environmental factors may be important in the pathogenesis of PFAPA syndrome and should be evaluated in future studies. What is Known: • The pathogenesis and genetics of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome remain unsolved. • PFAPA syndrome has been shown to cluster in families. What is New: • Maternal smoking and lack of breastfeeding are more common in patients with PFAPA syndrome than in the controls. • Environmental risk factors may be important in the pathogenesis of the syndrome.

Severe Disseminated Necrotizing and Granulomatous Lymphadenitis and Encephalitis in a Dog Due to Sporotrichum pruinosum (Teleomorph: Phanerochaete chrysosporium).

A 9-year-old female mixed breed dog presented for an acute onset of anorexia, vomiting, and cough. Initial examination and diagnostics revealed a large multilobular cranial mediastinal mass with unidentified fungal organisms on cytology. The disease progressed in spite of therapy until the dog was euthanized 8 months later. Gross necropsy findings were a large multilobular intrathoracic mass, mild pleuritis, and generalized lymphadenopathy. Histologic evaluation showed granulomatous inflammation and necrosis with numerous 20- to 70-micron, periodic acid-Schiff- and Gomori methenamine silver-positive spherules effacing lymph node parenchyma, as well as severe inflammation within the midbrain. Endosporulation was a common finding, and large numbers of fungal hyphae were also present in affected areas. Ribosomal RNA gene sequencing found 100% identity to published sequences of Phanerochaete chrysosporium, the teleomorph form of Sporotrichum pruinosum. This is the first published report of disease caused by natural infection with this basidiomycete organism in animals.

Cernunnos deficiency associated with BCG adenitis and autoimmunity: First case from the national Iranian registry and review of the literature.

Non-homologous end-joining (NHEJ) is a pathway that repairs double-strand breaks (DSB) in DNA and plays a vital role in V(D)J recombination of immunoglobulin genes. Cernunnos is a DNA repair factor that is involved in nonhomologous end-joining (NHEJ) process. Impairment in Cernunnos leads to a genetic disease characterized by neural disorders, immunodeficiency and increased radiosensitivity. We herein describe a severe combined immunodeficiency (SCID) patient with T- B+ phenotype who had a mutation in Cernunnos gene and manifested recurrent infections, microcephaly and growth retardation with hypogammaglobulinemia. Furthermore, our patient was associated with BCG adenitis and autoimmunity that less is observed in patients with Cernunnos deficiency. In contrast to previous reported Cernunnos-deficient patients, our patient had normal B-cell number along with normal IgA and IgM, suggesting a leaky form of the Cernunnos deficiency due to residual count of B cells in our patient. Cernunnos deficiency should be considered in children with recurrent bacterial infections, microcephaly and growth retardation, in spite of having normal B-cell as well as normal IgM and IgA level.

Far-infrared ray for treating chronic lower extremity lymphedema with dermatolymphangioadenitis: a postoperative complication of gynecological tumor resection.

PURPOSE: Lower extremity lymphedema is regarded as a relatively common postoperative complication and is often accompanied with dermatolymphangioadenitis (DLA). This study combines clinical assessment and laboratory investigation to explore therapeutic effects of far-infrared radiation (FIR) therapy for chronic lower extremity lymphedema accompanied with DLA, occurring after gynecological tumor resection. METHODS: Patients who met inclusion and exclusion criteria would be enrolled. They received regular sessions using the FIR therapy machine over the 4-week treatment course. Clinical and laboratory outcome measures were carried out before and after treatment. Clinical outcome measures included DLA seizure frequency (episodes/year), patients' subjective feedback for lymphedema-related symptoms and quality of life (QOL). Laboratory outcome measures included bacterial cultures and concentrations of inflammatory cytokines: IL-1ß, IL-2, IL-4, IL-10, IL-12, IL-18, TNF-α, TNF-ß, caspase-1 and INF-γ, detected in serum and local lymphedema tissue fluid samples using protein microarray and ELISA. RESULTS: Between 2012 and 2016, a total of 120 female patients were screened for study enrollment. Sixty-four recruited patients underwent clinical evaluation both before FIR radiation therapy and 1 year after a single course of FIR radiation therapy. Eleven patients (17.2%), randomly chosen from the study group, underwent additional laboratory analysis of blood and local lymphedema tissue fluid samples. The frequency of DLA decreased following treatment (p < 0.001). Fifty patients (78%) did not experience a single episode of DLA recurrence in the year subsequent to treatment. The efficiency rate calculated using DLA frequencies was greater than 50% for 63 (98%) patients following treatment. Patients reported a subjective decrease in lymphedema-related symptoms (p < 0.05). Patients' QOL scores were higher after treatment (p < 0.001). Laboratory analysis showed an elevation in serum concentration of IL-1ß after FIR therapy (p < 0.05) and reduced local tissue fluid concentrations of inflammatory cytokines IL-2, IL-10 and IL-18 (p < 0.05). Bacterial culture results before and after treatment were both negative. CONCLUSION: FIR radiation therapy provides an effective treatment modality for patients with chronic lymphedema accompanied with DLA that develops secondarily to treatment of gynecological malignancies, whose therapeutic effects may be due to reduced immune dysfunction within local lymphedema tissues.

Paracoccidioides brasiliensis-associated dermatitis and lymphadenitis in a dog.

Paracoccidioidomycosis (PCM) is an endemic disease of humans from Latin America that is caused by Paracoccidioides brasiliensis and P. lutzii, with most cases of PCM in domestic animals being associated with P. brasiliensis. This study presents the clinical, cytological, mycological, serological, and molecular findings associated with P. brasiliensis in a dog from Southern Brazil. Fine needle biopsies were collected from the skin and several lymph nodes of a 5-year-old female Labrador dog that had enlargement of most superficial lymph nodes. Cytology of the skin and lymph nodes revealed pyogranulomatous dermatitis and lymphadenitis associated with fine-necked, budding fungal structures consistent with the Paracoccidioides genus of organisms; mycological culture derived from the lymph node aspirate demonstrated similar budding structures. Serological assays using exoantigens obtained from the fungal culture demonstrated that the fungal organisms derived from the lymph node were antigenically similar to P. brasiliensis by immunodiffusion and Western blot. A PCR assay, using the fungal culture as input, amplified a partial segment of the internal transcribed spacer 1 and 2 regions of P. brasiliensis; direct sequencing and phylogenetic analyses confirmed the PCR product as P. brasiliensis. The combined cytological, mycological, serological, and molecular findings confirmed a diagnosis of fungal dermatitis and lymphadenitis due to P. brasiliensis in this dog. This case represents the third description of clinical PCM in dogs and the first confirmation of mycotic dermatitis associated with P. brasiliensis in this species. The participation of dogs in the possible dissemination of PCM is reviewed, and it is proposed that dogs are probable accidental hosts in the epidemiological cycle associated with P. brasiliensis.

[CAUSES AND WAYS OF THE NECK PHLEGMON SPREADING ON MEDIASTINUM WITH A DESCENDING PURULENT MEDIASTINITIS OCCURRENCE].

Results of treatment in 2000-2016 yrs of 183 patients for the neck phlegmon were analyzed. In 60 (32.8%) of them a descending purulent mediastinitis (DPM) was diagnosed. The main causes of the DPM occurrence were tonsilogenic and odontogenous factors. Postoperative lethality in DPM have constituted 25%.

Novel insights into the early histopathogenesis of immunodeficiency-associated Burkitt lymphoma: a case report of Burkitt microlymphoma arising within HIV lymphadenitis.

AIMS: To report a case detailing the early histopathogenesis of Burkitt lymphoma (BL), Epstein-Barr virus (EBV) positive, in the clinical setting of HIV infection. METHODS AND RESULTS: We describe a 57 year-old woman with newly diagnosed HIV infection who presented with unilateral localized axillary lymphadenopathy. Histopathological, immunohistochemical, and flow cytometric analyses were performed and showed EBV-positive nests of Burkitt cells, including rare nests also positive for cytomegalovirus, exclusively located within hyperplastic monocytoid B-cell areas of HIV lymphadenitis. Due to positron emission tomography/computed tomography findings of persistent localized lymphadenopathy with markedly increased fludeoxyglucose avidity a core needle biopsy was performed. Histopathological, immunohistochemical, fluorescence in situ hybridization, and flow cytometric analyses confirmed BL. CONCLUSIONS: Early histopathogenesis of HIV-associated BL occurred as nests of EBV-positive Burkitt cells within prominent monocytoid B-cell areas in our case. The results equip the pathologist to identify a very subtle Burkitt microlymphoma which would allow for prompt and appropriate chemotherapeutic intervention and may promote research into the possible relationship between monocytoid B cells and BL.

Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis.

PFAPA syndrome represents the most common cause of recurrent fever in children in European populations, and it is characterized by recurrent episodes of high fever, pharyngitis, cervical adenitis, and aphthous stomatitis. Many possible causative factors have been explored so far, including infectious agents, immunologic mechanisms and genetic predisposition, but the exact etiology remains unclear. Recent findings demonstrate a dysregulation of different components of innate immunity during PFAPA flares, such as monocytes, neutrophils, complement, and pro-inflammatory cytokines, especially IL-1ß, suggesting an inflammasome-mediated innate immune system activation and supporting the hypothesis of an autoinflammatory disease. Moreover, in contrast with previous considerations, the strong familial clustering suggests a potential genetic origin rather than a sporadic disease. In addition, the presence of variants in inflammasome-related genes, mostly in NLRP3 and MEFV, suggests a possible role of inflammasome-composing genes in PFAPA pathogenesis. However, none of these variants seem to be relevant, alone, to its etiology, indicating a high genetic heterogeneity as well as an oligogenic or polygenic genetic background.

BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics.

BACKGROUND: When administered to an immune-compromised patient, BCG (Bacille Calmette-Guérin) can cause disseminated and life-threatening infections. OBJECTIVE: To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. MATERIALS AND METHODS: We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. RESULTS: Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. CONCLUSION: BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency.

Localized Subcarinal Adenitis following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for the diagnosis of mediastinal lymph nodes and masses. Its complications are rare and include hemorrhage, pneumothorax and infections such as mediastinitis. We report the case of a 51-year-old patient who presented with a localized subcarinal adenitis after EBUS-TBNA. Germs colonizing the oropharynx may have been dragged along by the echobronchoscope, inoculating the punctured mediastinal lymph node.