Lymphadenopathy in Children PDF

Lymphadenopathy in Children Pediatric Department 1 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES | TITLE 1. Lymph nodes in a healthy child (slides 3-13) 2. Diagnostic approach (objective examination) (slides 14-29) 3. Lab...

Lymphadenopathy in Children Pediatric Department 1 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES | TITLE 1. Lymph nodes in a healthy child (slides 3-13) 2. Diagnostic approach (objective examination) (slides 14-29) 3. Laboratory tests and treatment (slides 30-37) 4. Analysis of clinical cases (slides 38-57) LITHUANIAN UNIVERSITY OF HEALTH SCIENCES | TITLE 2 Lymphatic system Lymph Lymphatic vessels Central (primary) lymphatic organs: Bone marrow Thymus Peripheral (secondary) lymphatic organs: Lymph nodes, Spleen, Tonsils, adenoids, Peyer patches, Lymphoid tissues  The function of the lymphatic system Maintains the fluid balance in the body Participates in transport of the nutrients. Participate in the immune response To transport the antigen presenting cells to lymph nodes, where the immune response is stimulated Eliminates cells’ waste products and abnormal cells  Circulation of the lymph Plasma is filtered from blood capillaries into intracellular space The biggest part is reabsorbed to blood circulation The rest collect antigens, debris and is reabsorbed to lymphatic vessels  The structure of the lymph node Afferent vessels Capsule Trabecula Cortex (B lymphocytes layer) Deep cortex (paracortex) – T lymphocytes layer Medulla – B lymphocytes layer Efferent vessel  Normal lymph node Normal -Round or oval -Non-tender, non-fixed, soft and mobile Up to 1 cm in diameter in neonates In older children and adults: Inguinal l/n up to 1,5 cm Preauricular, epitrochlear up to 0,5 cm Others up to 1 cm 1.Spi jkers S, Littooij AS, Nievelstein RAJ. Measurements of cervi cal l ymph nodes in children on computed tomography. Pediatr. Radio. 2020; 50(4): 534–42 2. Locke R, Comfort R, Kubba H. When does an enlarged cervical lymph node in a child need excision? A s ys tematic review. Int. J. Pediatr. Otorhinolaryngol. 2014; 78: 393–401.  Epidemiology Palpable lymph nodes - very common in children The lymph nodes can be palpable in 38-45% of children without any evidence of underlying disease¹΄² The inguinal lymph nodes can be palpable in 1/3, and cervical lymph nodes – in 50 % of infants. 1. La rs son L.O., Bentzon M.W., Berg K., Mellander L., Skoogh B.E., Stranegœrd I.L. Palpable l ymph nodes of the neck i n Swedish schoolchildren. Acta Pa ediatrica. 1994;83:1092–1094 2. Ra jasekaran K, Kra kovitz P. Enlarged neck l ymph nodes i n children. Pediatr. Clin. North Am. 2013 3. Ba mji M, Stone RK, Ka ul A, Us mani G, Schachter FF, Wasserman E. Pa lpable lymph nodes i n healthy newborns and infants. Pediatrics 1986; 78: 573–5.  Lymphadenopathy Lymph node enlargement caused by infection, malignancy or other diseases. Pathophysiology of lymphadenopathy: Activation and proliferation of lymphocytes Infiltration of inflammatory cells Infiltration of neoplastic cells Neoplastic proliferation of lymphocytes or macrophages (leukemia, lymphoma) Infiltration of metabolite deposits  Classification of lymphadenopathy Localized – one site of lymph nodes is affected Systemic or generalized – two or more sites of lymph nodes are affected Acute – with the duration less than 2 weeks Subacute – duration from 2 to 6 weeks Chronic – more than 6 weeks Oguz A, Karadeniz C, Temel EA, Citak EC, Okur FV. Evaluation of peripheral lymphadenopathy in children. Pediatr Hematol Oncol. 2006 Oct-Nov. 23(7):549-61  Causes of lymphadenopathy Infection: Bacteria – Streptococcus A gr (nose, throat, ear) , Staphylococcus Aureus (skin), Tuberkulosis, B. henselae Virus – Herpes, Adenovirus, Rubella, Mumps Protozoal – Toxoplasmosis Fungal infection-blastomycosis, Histoplasmosis Autoimmune disease - lupus, juvenile rheumatoid arthritis, chronic granulomatous disease Metabolic disease-Goshe , Niemann-Pick disease Malignancy – Lymphoma, leukaemia ir solid tumours with metastases Other - sarcoidosis, hemophagocytic Lymph histiocytosis AKC Leung et al. Cervi cal l ymphadenitis:Etiology, diagnosis and management. Curr Infect Dis Rep. 2009; 11(3): 183–189.  Studies Authors Years of N of patients Causes publications Infection Oncology Venturini E et al.* 2020 322 155 (49,4%) 4 (1,2%) Sarsu SB et al.** 2016 1700 455 (26,7%) 40 (2,3%) Bozlak S et al*** 2016 218 90 (41,3%) 6 (2,7%) Infections: Oncology: EBV-27-29% Strept. 10-25% Lymphomas 60-70%, leukaemia, histiocytosis Atypical mycobact 17,6% Toxoplasmosis 11% CMV 4% * Venturini E et a l. Clinical features and outcomes of lymphadenopathy i n a tertiary children's hospital. J Pa ediatr Child Health. 2020 Ma y 21. doi:10.1111/jpc.1492. **Sa rs u SB, Sahin K. Retrospective evaluation of lymphadenopathy i n children i n a single center's experience. J Pa k Med Assoc. 2016 Jun;66(6):654-7. ***Bozl ak S et al. Cervi call ymphadenopathies i n children. A prospective clinical cohort study. Int J Pediatr Otorhinolaryngol. 2016 Ma r; 82:81-7. 13 Lymphadenopathy: diagnostic challenge Lymphadenopathy is common and usually benign and self- limited. Enlargement of the lymph nodes can be a manifestation of serious disease. The challenge: ✓ to avoid aggressive evaluation and biopsy of most children; ✓ to make the diagnose of serious underlying disease in time. The decision depends: ✓ General condition of patient. ✓ Suspicion of the malignancy History of disease Lymphadenopathy onset and duration, applied treatment and its effect Previous symptoms of infection Constitutional symptoms Infections in environment Exposion with animals Tick, flea, mosquitoes bites Travel Sexual activity Medication history Immunization status and recent vaccines History of other chronic and acute illness Lymphadenitis after BCG  Objective examination Complete examination: Fever, body complection Palor, rash; Size of the liver and spleen Auscultation of the lungs and heart The organs drained by enlarged lymph node(s): Throat Mouth and teeth Skin and soft tissue CJ Twi s t, MP Li nk. Assessment of Lymphadenopathy i n Children.2002 Oct;49(5):1009-25. Oguz A, Ka ra deniz C, Temel EA, Ci tak EC, Okur FV. Eva luation of peripheral l ymphadenopathy i n children. Pediatr Hematol Oncol. 2006 Oct-Nov. 23(7):549-61.  General symptoms Fever > 1 week (witout the signs of infection) Weight loss > 10 % Night sweating Somnolence, malaise Skin itching, bone pain Signs of lymphoma, other malignancy or serious systemic infections or autoimmune diseases Tonsilitis + reactive lymhadenopathy Stomatitis Cat scratch Panaritium (whitlow) Size and consistency of the lymph nodes Size: Normal lymph nodes are less than 1 cm; Epitrochlear and preauricular region < 0.5 cm Inguinal region < 1.5 cm. Normal lymph nodes tend to be larger in childhood (ages 2-10 y) than later in life. The risk of malignancy is increased in lymph nodes >2 cm in diameter, although malignancy may occur in smaller nodes Consistency: Normal - soft, freely mobile Fluctuance usually indicates infection within the node; Fibrotic nodes are due to cancer or chronic inflammation. Firm, rubbery nodes may indicate lymphoma or chronic leukemia. Lymph node in the posterior neck region  Tenderness Healthy lymph node is non-tender Infected or inflamed lymph node became very painful. Tenderness occurs because of hemorrhage into a lymph node or immunologic stimulation. Malignant lymph node is usually non-tender.  Local lymphadenopathy Cat scratch disease Eye, skin infection, toxoplasmosis Scalp infection, pediculose Rubella Streptococcal infection (nose, throat) Dental and mouth infection Viral infection (EBV, CMV, toxo) TBC Malignancy (lymphoma) Karadeniz C, Oguz A, Ezer U, Oztürk G, Dursun A. The etiology of peripheral lymphadenopathy in children. Pediatr. Hematol. Oncol. 1999; 16: 525–31. Supraclavicular lymph node  Local lymphadenopathy Local infection (Staphylococcus) Malignancy (lymphoma, neuroblast.) Cat scratch disease TBC Mesiadenits Lymphoma Skin infection Sexual. trans.d. Karadeniz C, Oguz A, Ezer U, Oztürk G, Dursun A. The etiology of peripheral lymphadenopathy in children. Pediatr. Hematol. Oncol. 1999; 16: 525–31.  Generalized lymphadenopathy Generalized lymphadenopathy Inflammation Malignancy Systemic Autoimmune Primary - Methastatic-leukaemia, infection disease lymphoma neuroblastoma rabdomiosarkoma Infant- Child-CMV, Lupus, juvenile toxoplasmosis, EBV, artrhritis, CMV, HIV, syphyllis toxoplasmosis sarcoidosis Yaris N, Cakir M, Sozen E, Cobanoglu U. Analysis of children with peripheral lymphadenopathy. Clin Pediatr (Phila). 2006 Jul. 45(6):544-9.  Laboratory tests Complete blood count (CBC) and differencials (periferal blood smear) Markers of inflammation (CRB, ENG) Biochemic tests – liver function, LDH – as lymphoproliferative marker, ASO titer Bacterial and fungal culture (throat, blood, skin lesions, abscess and fluctuant lymph nodes) Serology (EBV, CMV, Toxo, Bartonella henselae) Tuberculin skin test (TST) Instrumental tests: Sonography – lymph nodes, abdominal Chest Xray, or CT Biopsy  Chest Xray Performed in children with: Generalized lymphadenopathy; Supraclavicular of infraclavicular lymphadenopathy; Localized lymphadenopathy ≥ 2 cm (no signs of infection; no response to antimicrobial therapy). The changes that are most commonly found: Mediastinal mass (lymphoma, neuroblastoma and other malignancy) Hilar adenopathy (sarcoidosis, tuberculosis, Hodgkin lymphoma) Other CXray findings that may be helpful in determining the cause of lymphadenopathy Chest Xray  Sonography Affected lymph node: To define the presence and extent of an abscess To differenciate malignant from infectious lymph nodes To distinguish the lymph node from other abnormality Abdominal US: children with unexplained lymphadenopathy: looking for abdominal masses abdominal lymphadenopathy Ultrasound  Indications for biopsy Urgent biopsy: Suspicion of malignancy: Lymph node > 2 cm No signs of infection Supraclavicular or infraclavicular lymphadenopathy Mediastinal lymphadenopathy Delayed biopsy (after 4-6 weeks): Lymph node does not decrease after treatment or observation Dorfman T, Neymark M, Begal J, Kluger Y. Surgical Biopsy of Pathologically Enlarged Lymph Nodes: A Reappraisal. Isr. Med. Assoc. J. 2018 Nov;20(11):674-678.  Biopsy Open exisional biopsy of lymph node is prefered to aspiration. The selection for biopsy: The most abnormal lymph node. Supraclavicular Cervical Axillary Inguinal  Treatment approach No suspicion of malignancy Antibiotic therapy, if bacterial infection is suspected or approved: Penicillin group antibiotics (amoxicillin) First-generation cephalosporin (cefalexin, cefazolin) 10-14 days Azithromycin must be prescribed for patients with cat scratch disease. Viral infection – symptomatic treatment Observation for 2 – 4 weeks (decision for biopsy)  Analysis of clinical cases Lymphadenopathy Reaction to danger signal Lymphadenitis Reactive lymphadenopathy Malignant lymph node Oguz A, Ka ra deniz C, Temel EA, Ci tak EC, Okur FV.c Eva luation of peripheral l ymphadenopathy i n children. Pediatr Hematol Oncol. 2006 Oct-Nov. 23(7):549-61. Male 6 years Ultrasound Lymphadenitis Infection in the lymph node Febrile Localized lymphadenopathy > 3 cm in diameter Extremely painful Fluctuant Edema and redness of the skin Elevated markers of inflammation in blood test L/n ultrasound – suppuration, and active blood perfusion. https://www.msdmanuals.com/home/skin-disorders/bacterial-skin- infections/lymphadenitis Male 10 years Ultrasound of the lymph nodes Chest Xray  Malignant lymph node Slowly growing (takes few weeks-months) The large lymph node (> 2 cm) or group of lymph nodes Localized or generalized Firm, fibrotic, fixed Non-tender Ca limfmazgis Lymphadenopathy progress regardless treatment or observation General symptoms (fever, weight loss, fatigue, sweating, bone pain, itching of the skin) are common. Blood count is non-specific, exception – leukemia. Male 7 years  Reactive lymphadenopathy L/n enlargement because of immune stimulation Common in children Mostly found in the neck Bilateral enlargement of l/n (up to 1,5- 2 cm in diameter) Non-tender Soft, mobile Usually improves after few weeks Can persist few years after infection https://www.gponline.com/paediatric-medicine-tonsillitis-children/ear-nose-and-throat/ear-nose-and-throat/article/1024856 Male 15 years Male 15 years WBC 17.03 x10*9/l NEUT 11.1% RBC 3.05x10*12/l LYMPH 78.1% HGB 98 g/l MONO 8.8 % EOS 2.0 % HCT 26.8% CRB < 3 mg/l MCV 83.1fl Ret 1,2% MCH 25.8pg RDW 14.4% PLT 83 x10*9/l Peripheral blood smear - mononucleosis Atypical mononuclears  Remarks Lymphadenopathy in children is often benign and self-limiting Anamnesis and objective examination are important and sufficient to detect the cause of lymphadenopathy in the beginning Additional tests must be performed in case of acute infection or suspicion of serious systemic disease (e.g., malignancy) Observation and repeated examination after 4 – 6 weeks is absolutely necessary. Even the malignant lymph node in children is rare, it is relevant to look at worrisome symptoms and to suspect cancer in time