Isolated Nodal TBC Reactivation in a Patient with Post-Thrombocythemia Myelofibrosis Treated with Ruxolitinib: Case Report and Review of the Literature.

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases describing TBC reactivations in MF patients assuming ruxolitinib and successfully treated with 4-drug anti-TBC therapy are available in the literature to date. The case we reported describes an isolated lymph nodal TBC reactivation in a patient with the diagnosis of post-essential thrombocythemia-MF during ruxolitinib treatment after a long course of interferon-a (IFN-α2b) assumed for the previous diagnosis of ET. The case we report teaches that lymphadenopathy with or without constitutional symptoms developing during ruxolitinib therapy should be considered as a possible manifestation of a TBC reactivation in patients with a previous positive TBC-exposure test. In these cases, Ziel-Nielsen testing on urine and sputum has to be performed to rule out infectiousness and eventually isolate the patient. Moreover, previous long-time exposition to IFN-α2b may be related with a higher risk for TBC reactivation in these subset of patients. We encourage reevaluation of the cohorts of patients treated with ruxolitinib in previous and current large prospective studies to study the possible correlation between previous exposition to IFN-α2b and TBC reactivation.

Diagnosis and Management of Children With Mycobacterium abscessus Infections in the Head and Neck.

PURPOSE: Controversy exists regarding the most appropriate treatment strategy for children with nontuberculous mycobacterial (NTM) cervical lymphadenitis. Mycobacterium abscessus (MAB) is an uncommon cause of NTM cervical lymphadenitis. The purpose of the present study was to evaluate diagnosis, management, and treatment outcomes in children with MAB-associated cervical lymphadenitis resulting from a pulpotomy. MATERIALS AND METHODS: This was a retrospective chart review of children with NTM lymphadenitis of the head and neck caused by MAB treated at Children's Healthcare of Atlanta hospitals (Atlanta, GA). The predictor variables were patient demographics, dental history, clinical presentation, imaging characteristics, laboratory findings, histopathologic examination, treatment, and complications. The outcome variable was disease resolution or persistence. RESULTS: Twenty-two patients (mean age, 6.5 yr) met the inclusion criteria. All patients had pulpotomy at 1 dental practice. The mean time from dental procedure to symptom onset was 43.1 days (range, 3 to 180 days). Children presented with cervical or submandibular swelling, facial swelling, gingival erythema, and skin erythema. Radiographic findings were submandibular or cervical lymphadenitis, maxillary or mandibular osteolysis, subcutaneous abscess, and pulmonary nodules. All children had confirmed or probable MAB infection diagnosed on the pathologic specimen. There were 2 distinct patient presentations that guided surgical management: isolated noninflammatory cervical lymphadenitis, which was partly or completely excised (n = 11), and adjacent extension or disseminated infection requiring subtotal lymph node excision, bone debridement, and postoperative antibiotics (n = 11). Most children required multiple surgical interventions to remove infected tissues. All achieved clinical resolution. CONCLUSION: In this cohort, treatment of NTM lymphadenitis caused by MAB depended on extent of disease and virulence of bacteria. When complete surgical excision was possible, disease resolution was achieved. However, in cases with adjacent extension or dissemination infection, postoperative antibiotics were necessary.

BCG-SSI(®) vaccine-associated lymphadenitis: Incidence and management.

BACKGROUND AND OBJECTIVE: There is a high incidence of childhood tuberculosis in Latvia, including children aged less than 1 year, while BCG-associated lymphadenitis is one of the most frequent adverse events requiring surgical treatment. The aim of this study was to analyze the incidence of purulent BCG adenitis through-out the population of Latvia after the introduction of BCG-SSI(®) vaccine and to evaluate the treatment results. MATERIAL AND METHODS: The study included 194 patients. All patients had received the BCG-SSI(®) vaccine during the first week of life routinely or at a later time according to the indications. The indications for surgical treatment were lymph node destruction also affecting the skin. All patients in this study received surgical treatment - the affected lymph node extirpation. RESULTS: The mean age of the patients was 5.12±0.96 months. A total of 172 patients had purulent axillar lymphadenitis, 14 had purulent supraclavicular lymphadenitis, 8 patients had lymphadenitis at both localizations. During the whole study period the incidence of BCG adenitis varied from 0.02% to 0.36%, while the mean rate was 0.11%±0.08% from 184,068 vaccinated children during the study period. We observed an increasing trend in the incidence of BCG lymphadenitis during the study period. The primary and complete healing rate at the end of period was 99.5% (n=193) following an affected lymph node extirpation. The mean hospitalization time after the operation was 3.71±0.18 days. CONCLUSIONS: The incidence of BCG-SSI(®) vaccine associated purulent lymphadenitis varied widely with an increasing trend, followed by the return to the product characteristic limits. Indications for the surgical treatment should not be changed. Extirpation of the purulent BCG adenitis is a safe treatment method and leads to the primary wound healing in the majority of cases.

Tuberculosis lymphadenitis in a well managed case of sarcoidosis.

Differentiation between tuberculosis (TB) and sarcoidoisis is sometimes extremely difficult. Sequential occurrence of sarcoidosis and TB in the same patient is uncommon. We present the case of a young man, with a proven diagnosis of sarcoidosis who later developed TB after completion of treatment for sarcoidosis. A 32-year-old male patient presented with low-grade fever since two months. Physical examination revealed cervical lymphadenopathy. Initial fine needle aspiration cytology (FNAC) of the cervical lymph node was suggestive of granulomatous inflammation; the chest radiograph was normal. Repeat FNAC from the same lymph node was suggestive of reactive lymphoid hyperplasia. The patient was treated with antibiotics and followed-up. He again presented with persistence of fever and lymphadenopathy and blurring of vision. Ophthalmological examination revealed uveitis, possibly due to a granulomatous cause. His repeat Mantoux test again was non-reactive; serum angiotensin converting enzyme (ACE) levels were raised. This time an excision biopsy of the lymph node was done which revealed discrete, non-caseating, reticulin rich granulomatous inflammation suggestive of sarcoidosis. The patient was treated with oral prednisolone and imporved symptomatically. Subsequently, nearly nine months after completion of corticosteroid treatment, he presented with low-grade, intermittent fever and a lymph node enlargement in the right parotid region. FNAC from this lymph node showed caseating granulomatous inflammation and the stain for acid-fast bacilli was positive. He was treated with Category I DOTS under the Revised National Tuberculosis Control Programme and improved significantly. The present case highlights the need for further research into the aetiology of TB and sarcoidosis.

[A clinical study on 8 cases of sarcoidosis with a cervical mass as a symptom].

Sarcoidosis is a multiorgan granulomatous disease of unknown origin, which frequently involves the lung and the eyes. It is rare that sarcoidosis causes cervical lymphadenopathy and a chronic continuous salivary gland swelling. In the present study, we examined how to diagnose sarcoidosis in patients complaining of a cervical mass and its clinical presentation according to 8 cases which we experienced. We undertook biopsy of the cervical lymph nodes in 7 cases, and biopsy of the parotid gland in 1 case. In cases non-caseating epithelioid cell granuloma was proved, diagnosed as sarcoidosis histopathlogically. In 6 patients, the sarcoidal lesion was in other organs, whereas in 2 patients the sarcoidal lesion was confined in the head and neck. Bilateral hilar lymphadenopathy and an elevated level of angiotensin-converting enzyme which are typical in sarcoidosis were confirmed in only one of our patients. Therefore, the diagnostic value of these tests is low for the diagnosis of sarcoidosis in the patients whose chief complaint is a cervical mass. Because 4 out of 7 cases were positive for the tuberculin test, it is imperative to distinguish between sarcoidosis and cervical tuberculous lymphadenitis by combining the culture of acid-bacilli and TB-PCR with histopathological evaluation of the biopsy specimen. We experienced one patient in whom the sarcoidal lesion developed in the skin and the eyes 20 years after the onset of cervical lymphadenopathy. It is important to follow the patients carefully, even if we diagnose the disease as sarcoidosis confined in the head and neck.

[A 76-year-old female patient with deep venous thrombosis and cervical lymphadenopathy]. / 76-jährige Patientin mit tiefer Beinvenenthrombose und zervikaler Lymphadenopathie.

We report the case of a 76-year-old female patient presenting with deep venous thrombosis and upper cervical lymphadenopathy. A computed tomography (CT) scan showed multiple hepatic lesions with a high suspicion of metastatic disease from an unknown primary tumor. The differential diagnosis of lymphadenopathy and hepatic lesions includes malignant tumors and various infectious diseases. The diagnostic process, however, revealed lymph node tuberculosis with multiple hepatic granulomas despite a repeatedly negative interferon-γ release assay. A combined antituberculosis therapy led to complete clinical remission.

Knowledge of cervical tuberculosis lymphadenitis and its treatment in pastoral communities of the Afar region, Ethiopia.

BACKGROUND: Infection with Mycobacterium bovis (Mb) predominantly causes cervical TB lymphadenitis (TBL). Raw milk is considered the main source of Mb infection and raw milk is a major food source for Afar pastoralists. The aim of this study was to assess Afar pastoralists' knowledge concerning cervical TBL and its treatment. METHODS: A community-based cross-sectional survey involving 818 interviewees was conducted in two districts of the Afar Region, Ethiopia. In addition, two focus group discussions (FGDs) were conducted in each of the study areas, one with men and the other with women. RESULTS: Of the 818 interviewees [357 (43.6%) females and 461 (56.4%) males], 742 (90.7%) reported that they had knowledge of cervical TBL, mentioning that swelling(s) on the neck resulting in a lesion and scar are common symptoms. However, only 11 (1.5%) individuals mentioned that bacteria or germs are the causative agents of TBL. Three interviewees and a male discussant mentioned drinking raw milk as the cause of TBL. A considerable proportion (34.2%) of the interviewees and almost all the discussants suggested herbal medicine as an effective treatment. Male study participants were 1.82 times more likely to have overall knowledge of TBL than female study participants (adjusted OR, 1.82; 95% CI, 1.32 to 2.51, p < 0.001). CONCLUSION: The pastoral community members in the study areas had little biomedical knowledge of the cause, the source of infection and the transmission route of cervical TBL. Furthermore, most community members believed that herbal medicines are the most effective treatment for TBL. Therefore, TB control programs in the Afar Region require the incorporation of public health education introducing current biomedical knowledge of the disease. In addition, further studies are important to elucidate which medicinal plants are used by Afar pastoralists to treat TBL.

[Development of cervical tuberculous lymphadenitis in a patient with Crohn's disease receiving infliximab despite of chemoprophylaxis with isoniazid].

We herein report a case of a 41-year-old female with a 14-year history of Crohn's disease who had been treated with diet and mesalazine. Because of inadequate control, therapy with infliximab was planned. She had a positive result on the interferon-gamma release assay (QuantiFERON TB). After active tuberculosis was ruled out by chest x-ray and computed tomography, she was started on a six-month course of isoniazid 7 weeks prior to starting infliximab. After 10 doses of infliximab (15 months of therapy), she presented with pain of cervical lymphadenopathy. A biopsy of the lymph nodes revealed Langhans giant cells from granulomas and a positive result of polylmerase chain reaction for Mycobacterium tuberculosis. The treatment with infliximab was discontinued and anti-tuberculosis therapy was started. Although treatment for latent tuberculosis infection lowers the risk of reactivation of tuberculosis due to tumor necrosis factor alpha-blockers, it cannot completely inactivate tuberculosis. Despite the completion of chemoprophylaxis, patients receiving such agents should be instructed to watch out for any symptoms associated with pulmonary and extrapulmonary tuberculosis such as fever, cough, malaise, body weight loss, night sweating and lymphadenopathy, and they should also be closely followed up.

Myocardial tuberculosis and beyond: A rare form of extra pulmonary TB in a young boy.

Myocardial tuberculosis is an exceptionally rare form of extra-pulmonary TB. Few cases were reported world-wide. Here a young snake charmer who had skin tuberculosis 5 yrs back admitted into National institute of diseases of Chest and hospital (NIDCH), Dhaka with the complaints of cough, palpitation and breathlessness for 2 months. He had right axillary firm matted lymphadenopathy, left sided large pleural effusion, left ventricular and septal hypertrophy with band and mass inside the ventricle (evident on CT scan of heart and echocardiography). His ESR was 95 mm in1st hr, Mantaux test was 15mm, Pleural fluid was exudative lymphocyte predominant with adenosin deaminase (ADA) 68.6 U/L. Fine needle aspirates from right axillary LNs showed Mycobacterium tuberculosis on GeneXpert for MTB/RIF testing and caseous granuloma on cytopathological study. Whole Body F18 FDG PET-CT revealed numerous low FDG avid size significant lymph nodes in right side of neck, mediastinum and right axilla with cardiomegaly with focal FDG avid within the left ventricular cavity likely to be prominent papillary muscle. MRI of heart or Myocardial biopsy for histology was not done due to their cost and invasiveness and also for that there was sufficient evidence of having tuberculosis in lymph node, pleura nas myocardium. This patient was treated with anti tubercular medications (3HRZE2S/5HRE) with prednisolone for six months. After treatment, myocardial lesions, pleural effusion and lymphadenopathy were found resolved. Thus a case of fatal and serious tuberculosis was explored and managed successfully.

Mycobacterium haemophilum as a novel etiology of cervical lymphadenitis in an otherwise healthy adult patient.

We describe a case and summarize six additional cases of cervical lymphadenitis in otherwise healthy adults caused by Mycobacterium haemophilum. The organism causes cervicofacial lymphadenitis in healthy children and severe disease in immunocompromised patients but has not been previously reported to cause cervical lymphadenitis in nonimmunocompromised, healthy adults.

Unusual presentation of tuberculosis in an infliximab-treated patient--which is the correct TB screening before starting a biologic?

Infliximab is an anti-TNFalpha chimeric monoclonal antibody, commonly used in the treatment of moderate to severe psoriasis. TNFalpha is a pro-inflammatory cytokine which play a key role in host defense from infections by intracellular bacteria, such as Listeria monocytogenes, Histoplasma Capsulatum and especially Mycobacterium Tuberculosis. Infliximab therapy increases the risk of tuberculosis due mainly to the reactivation of latent TB infection (LTBI) and, therefore, it is mandatory to screen patients for LTBI prior to starting a treatment with anti-TNFalpha agents. We report the case of a psoriatic patient, who, despite a negative screening for infection by M. tuberculosis including both tuberculin skin test (TST) and chest X-ray, developed after 4 months of infliximab treatment, a severe pulmonary, lymphnodal and intestinal tuberculosis during infliximab treatment.

Bacillus Calmette-Guérin Cervical Lymphadenitis in a 6-Year-Old Boy on Infliximab for Inflammatory Bowel Disease.

We encountered a case of Bacillus Calmette-Guérin (BCG) cervical lymphadenitis in a patient undergoing infliximab after 6 years from BCG vaccination. Tumor necrosis factor-α inhibitors may be a risk for reactivation of BCG and serious infection even several years after vaccination.

[Disseminated infection caused by the bacillus Calmette-Guérin vaccine and SARS-CoV-2 coinfection in a patient with IL-12 receptor ß1 subunit deficiency]. / Infección diseminada por vacuna con bacilo de Calmette-Guérin y coinfección por SARS-CoV-2 en paciente con deficiencia de la subunidad ß1 del receptor de IL-12.

BACKGROUND: Inborn errors of immunity manifest with a greater susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, or malignancies. One of these is the mendelian susceptibility to mycobacterial disease. The most frequent etiology is the complete autosomal recessive deficiency of the ß1 subunit of the interleukin 12 receptor. CASE REPORT: A female patient who, by the age of six months, started with a nodular lesion in the right shoulder and ipsilateral axillary adenitis after the bacillus Calmette-Guérin vaccine was applied. Later, she developed a cutaneous fistula in the anterior thorax, the inframammary region, and chronic recidivant suppurative lymphadenitis. A disseminated infection caused by Mycobacterium bovis was diagnosed, therefore, individualized pharmacological treatment was required due to failure with the primary treatment. The patient was diagnosed with deficiency in the ß1 subunit of the interleukin 12 receptor at age six. During her last hospitalization, she presented fever, cough, and tachypnea, and SARS-CoV-2 was detected by quantitative polymerase chain reaction. The patient has had a favorable evolution. CONCLUSION: In patients with disseminated infections caused by bacillus Calmette-Guérin vaccination or by environmental mycobacteria, there should be suspicion of an inborn error of immunity and the patient should be referred to a third level hospital for an early immunological assessment.

Antecedentes: Los errores innatos de la inmunidad se manifiestan con una mayor susceptibilidad a infecciones, autoinmunidad, enfermedades autoinflamatorias, alergia o malignidad. Uno de estos es la susceptibilidad mendeliana a infecciones micobacterianas. La etiología más frecuente es la deficiencia completa autosómica recesiva de la subunidad ß1 del receptor de interleucina 12. Caso clínico: Paciente que comenzó a los seis meses de edad con una lesión nodular en hombro derecho y adenitis axilar ipsolateral posterior a la vacuna con bacilo de Calmette-Guérin. Posteriormente desarrolló una fistula cutánea en tórax anterior, región inframamaria y linfadenitis supurativa crónica recidivante. Se diagnosticó infección diseminada por Mycobacterium bovis, por lo que requirió tratamiento farmacológico individualizado debido al fracaso con el tratamiento primario. La paciente fue diagnosticada con deficiencia de la subunidad ß1 del receptor de interleucina 12 a los seis años. Durante su última hospitalización presentó fiebre, tos y taquipnea, detectándose SARS-CoV-2 por reacción en cadena de la polimerasa cuantitativa. La paciente evolucionó favorablemente. Conclusión: En los pacientes con infecciones diseminadas por la vacuna con bacilo de Calmette-Guérin o micobacterias ambientales, debe sospecharse un error innato de la inmunidad y derivarlos a tercer nivel de atención para la evaluación inmunológica temprana.

Lymphatic spread in an immunocompetent adult.

Cutaneous tuberculosis with lymphatic spread is rarely described. We report the case of a woman aged 38, immunocompetent, working in a fruit sorting center, who consulted us for ulceration of the left third finger that had persisted for four months, following a prick from a prickly pear. Physical examination revealed a nodular, erythematous, and ulcerative lesion of the left third finger, associated with inflammatory subcutaneous nodules arranged in a line along the ipsilateral upper extremity and an ipsilateral axillary lymph node. Laboratory tests and chest X-ray were normal. Pathological examination revealed granulomatous chronic inflammation without necrosis. PCR detected DNA from Mycobacterium tuberculosis. No extracutaneous tuberculosis locations were detected. A tuberculous chancre by direct inoculation was therefore diagnosed. The patient received quadruple therapy (rifampicin + isoniazid + pyrazinamide + ethambutol) for 2 months, followed by a combination therapy based on isoniazid and rifampicin for 6 months. Marked regression of the cutaneous lesions occurred after 1 month of first-line therapy. A tuberculous chancre is a rare form of cutaneous tuberculosis, with possible lymphatic spread, in immunocompromised patients but also in immunocompetent children and young adults.

Bacteriologically Determined De Novo Tuberculosis during Tumor Necrosis Factor-α Inhibitor Therapy.

A 58-year-old man with Crohn's disease received adalimumab for 13 months after screening results for tuberculosis were found to be negative. He was diagnosed with de novo mediastinal lymph-node tuberculosis, which was proved to be bacteriologically identical to that of an individual with smear positive lung tuberculosis by a variable number of tandem repeat analyses. After initiating anti-tuberculosis therapy, the patient developed immune reconstitution syndrome, which was improved by the re-administration of adalimumab. Even in countries with an intermediate tuberculosis burden, including Japan, we need to be alert for de novo tuberculosis as well as its reactivation during tumor necrosis factor-α inhibitor therapy.

Mycobacterium avium complex infection after alemtuzumab therapy for chronic lymphocytic leukemia.

Alemtuzumab is a humanized anti-CD52 monoclonal antibody indicated for treatment of fludarabine-refractory B-cell chronic lymphocytic leukemia (B-CLL). Severe lymphopenia is one of the most profound hematologic effects of alemtuzumab, often predisposing patients to infectious complications such as herpes simplex virus, cytomegalovirus, and Pneumocystis jiroveci pneumonia. Opportunistic infections secondary to mycobacterial sources have been documented less frequently. We describe the case of a 46-year-old man who developed a 40-mm lymph node mass 4 months after completing alemtuzumab therapy. After a thorough evaluation, he began treatment for tuberculosis with a four-drug combination regimen. The patient's final biopsy report indicated the presence of Mycobacterium avium complex. All clinical signs of the infection resolved with no recurrence. To our knowledge, this is the first published report of a patient who developed M. avium complex after alemtuzumab therapy. Consideration of primary prophylaxis against M. avium complex infections in aggressively treated patients with advanced B-CLL or other clinical indications may be warranted if future reports of such atypical infections emerge.

[Intestinal tuberculosis of the terminal ileum causing obstructive ileus and tuberculous peritonitis and presenting numerous peritoneal small red nodules: a case report].

A 38-year-old woman suffering from lower abdominal pain was referred to our hospital. Abdominal computed tomography showed marked thickening of the terminal ileum to the cecum, localized collection of ascites, and multiple mesenteric lymphadenopathy. A barium contrast small bowel series showed solitary severe stenosis of the terminal ileum with marked swelling of the ileocecal valve, where colonoscopy could not pass through, suggesting that ileal stenosis was caused by intestinal tuberculosis. She also showed strongly positive tuberculin skin test. Laparoscopy-assisted ileocecal resection was performed for confirmation of diagnosis and removal of the stenotic intestinal lesion. Laparoscopically, numerous small red nodules scattered on the stenotic ileal serosa, peritoneum, and mesenterium. Histopathological examination revealed ileal tuberculosis causing ulcerative stricture, and mesenteric tuberculous lymphadenitis. The small red nodules were formed of hemorrhagic tuberculous nodules.

Mediastinal ganglionar tuberculosis postcardiac transplantation.

The diagnosis and treatment of tuberculosis (TB) in transplanted receivers presents several challenges. TB is an opportunistic infection with high morbidity and mortality in solid organs of transplanted patients, therefore, the diagnosis difficulties. A case of a 30-year-old male, heart transplanted patient, who after being submitted to mediastinoscopy, obtained a result of lymph node TB.

A case report of granulomatous polyangiitis complicated by tuberculous lymphadenitis.

RATIONAL: Granulomatous polyangiitis (GPA) is a type of vasculitis involving medium and small arteries, typically affecting the upper and lower respiratory tract with coexisting glomerulonephritis. GPA is also characterized by necrotizing granulomatous inflammation and the presence of antineutrophil cytoplasm antibodies (ANCA). So far, various infections have lead to elevation of titers of serum ANCA, making it difficult to diagnose. PATIENT CONCERNS: We report a 50-year-old woman who was diagnosed as tuberculous lymphadenitis. During the treatment by anti-tuberculosis (TB) drugs, rapidly progressive renal failure and pleurisy had appeared with elevated titer of PR3-ANCA. Renal biopsy revealed crescentic glomerulonephritis. DIAGNOSIS: Renal biopsy revealed crescentic glomerulonephritis and diagnosis of GPA was made. INTERVENTIONS: Steroid therapy had been started with continuation of anti-TB drugs. OUTCOMES: Renal dysfunction had gradually recovered and pleurisy had disappeared with decreasing titer of PR3-ANCA. LESSONS: This is the first report of GPA complicated by TB infection. When we encounter a case with rapidly progressive renal failure during the TB infection, complication of GPA should be suspected as 1 of the different diagnosis.