Lymphadenopathy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Shyam Patel [2];Associate Editor(s)-in-Chief: Amandeep Singh M.D.[3], Raviteja Guddeti, M.B.B.S. [4] Ogechukwu Hannah Nnabude, MD
Synonyms and keywords: Lymph nodes enlarged; Enlarged lymph nodes; Lymphadenitis; Swollen lymph nodes; Swollen/enlarged lymph nodes
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Overview
Classification
Pathophysiology
Histopathology
Differentiating Lymphadenopathy from other Diseases
After a thorough history and physical examination, lymphadenopathy can be initially categorized as:
Diagnostic: wherein the practitioner has a proximal cause for the lymph nodes and can go on to treat them. Examples would be strep pharyngitis or localized cellulitis. The lymphadenopathy pattern history and physical examination can be suggestive an example would be mononucleosis wearing the practitioner has strong clinic index of suspicion can perform a confirmatory test which if positive he can go on and treat the patient.
Unexplained lymphadenopathy. Unexplained lymphadenopathy can be generalized into localized or generalized lymphadenopathy. Unexplained localized lymphadenopathy is further divided into patterns at no risk for malignancy or severe illness in which case the patient can be observed for 3 to 4 weeks and if response or improvement can be followed. The other alternative is if the patient is found to have a risk for malignancy or serious illness biopsy is indicated
Unexplained generalized lymphadenopathy can be approached after a review of epidemiological clues and medications with initial testing with a CBC with manual differential and mononucleosis serology if either is positive and diagnostic proceed to treatment. If both are negative, the second workup approach would be a PPD, and RPR, a chest x-ray, and ANA, hepatitis BS antigen serology, and HIV. Additional testing modalities and lab tests may be indicated depending on clinical cues. If the results of this testing are conclusive, the practitioner can proceed on to diagnosis and treatment of the illness. If the results of the testing are still not clear, proceed to biopsy of the most abnormal of the nodes. The most functional way to investigate the differential diagnosis of lymphadenopathy is to characterize it by node pattern and location, obtained pertinent history including careful evaluation of epidemiology, and place the patient in the appropriate arm of the algorithm to evaluate lymphadenopathy.
Generalized Lymphadenopathy
Common Infective Causation
- Mononucleosis
- HIV
- Tuberculosis
- Typhoid fever
- Syphilis
- Plague
Malignancies
- Acute leukemia
- Hodgkin's lymphoma
- Non-Hodgkin's lymphoma
Metabolic Storage Disorders
- Gaucher disease
- Niemann-Pick disease
Medication Reactions
- Allopurinol
- Atenolol
- Captopril
- Carbamazepine
- Cephalosporin(s)
- Gold
- Hydralazine
- Penicillin
- Phenytoin
- Primidone
- Pyrimethamine
- Quinidine
- Sulfonamides
- Sulidac
Autoimmune Disease
- Sjogren syndrome
- Sarcoidosis
- Rheumatoid arthritis
- Systemic lupus erythematosus
Localized Peripheral Lymphadenopathy
Head and Neck Lymph Nodes
Viral infection
- Viral URI
- Mononucleosis
- Herpes virus
- Coxsackievirus
- Cytomegalovirus
- HIV
Bacterial infection
- Staphylococcal aureus
- Group A Streptococcus pyogenes
- Mycobacterium
- Dental abscess
- Cat scratch disease
Malignancy
- Hodgkin disease
- Non-Hodgkin lymphoma
- Thyroid cancer
- Squamous cell carcinomas of the head and neck
Inguinal Peripheral Lymphadenopathy
Infection
- STDs
- Cellulitis
Malignancy
- Lymphoma
- Squamous cell carcinoma of genitalia
- Malignant melanoma
Axillary Lymphadenopathy
Infection
- Localized Staphylococcal aureus
- Cat-scratch disease
- Brucellosis
Malignancy
- Lymphoma
- Breast cancer
- Melanoma
- Reaction to breast implants
Supraclavicular Adenopathy
- Infections
- Mycobacteria
- Fungi
- Malignancy
Thoracic and abdominal neoplasms
- Hodgkin disease
- Non-Hodgkin lymphoma
Epidemiology and Demographics
Generalities can safely be made about the epidemiology of lymphadenopathy. [1] [2] [3]
First, both generalized and localized lymphadenopathies are fairly equally distributed without regard to gender.
Second, lymphadenopathy is more prevalent in the pediatric population than in the adult population secondary to the greater number of viral infections. It would follow that the majority of the time, lymphadenopathy in the pediatric population is of less consequence again secondary to the prevalence of viral and bacterial infections in that age group. Three-quarters of all lymphadenopathy observed are localized, and of those three-quarters, half of these are localized to the head and neck area. All remaining localized lymphadenopathy is found in the inguinal area, and the remaining lymphadenopathy is found in the axilla in the supraclavicular area. Of note, the differential diagnosis of lymphadenopathy changes significantly with the age of the patient.
Third, the patient's location and circumstance are very revealing and lymphadenopathy. For example, in the developing world (sub-Saharan Africa, Southeast Asia, Indian subcontinent), exposure to parasites, HIV, and miliary TB are far more likely to be causes of generalized lymphadenopathy then in the United States and Europe. Whereas, Epstein-Barr virus, streptococcal pharyngitis, and some neoplastic processes are more likely candidates to cause lymphadenopathy in the United States and the remainder of the localized industrial world. An exposure history is very important for diagnosis.
Exposure to blood and blood-borne products either through transfusion, unsafe sexual practices, intravenous drug abuse, or vocation Exposure to infectious disease whether it be travel, in the workplace, or the home Medication exposure-prescription, nonprescription, or supplements Exposure to animal-borne illness either via pets or the workplace Exposure to arthropod bites
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | Ultrasound | Other Diagnostic Studies
Laboratory Evaluation of Lymphadenopathy
- CBC with manual differential: This is a foundational test in the diagnosis of both generalized and regional lymphadenopathy. The number and differential of the white blood cells can indicate bacterial, viral, or fungal pathology. In addition, characteristic white blood cell (WBC) patterns are observed with several of the hematological neoplasms producing lymphadenopathy
- EBV serology: Epstein-Barr viral mono is present causing regionalized lymphadenopathy
- Sedimentation rate: A measure of inflammation though not diagnostic, it can contribute to diagnostic reasoning
- Cytomegalovirus titers: This viral serology is indicative of possible of CMV mononucleosis
- HIV serology: This serology can be used to diagnose acute HIV syndrome-related lymphadenopathy or to infer the diagnosis of secondary HIV-elated pathologies causing lymphadenopathy.
- Bartonella henselae serology: used for the diagnosis of cat-scratch lymphadenopathy
- FTA\RPR: These tests can diagnose syphilis as the cause of lymphadenopathy
- Herpes simplex serology: can determine if the lymphadenopathy is herpes-related. Herpes simplex can produce symptoms that are similar to mononucleosis.
- Toxoplasmosis serology: can be used to diagnose toxoplasmosis
- Hepatitis B serology: Serological tests for hepatitis B to establish it as a contributing factor for lymphadenopathy
- ANA: this is a screening test for SLE that can help establish it as a cause for generalized lymphadenopathy
Diagnostic Radiological Testing
- Chest x-ray: can reveal tuberculosis, pulmonary sarcoidosis, and pulmonary neoplasm.
- Chest CT scan: This modality of radiological imaging can define the above processes and reveal hilar adenopathy.
- Abdominal and pelvic CT scan: These images, in combination with chest CT scan, can be revealed in cases of supraclavicular adenopathy and the diagnosis of secondary neoplasm.
- Ultrasonography: can be used in the assessment of number, size, size, shape, the marginal definition, and internal structures in patients with lymphadenopathy. Color Doppler ultrasonography is of use in distinguishing the vascular pattern between more established, pre-existing lymphadenopathy and acute lymphadenopathy. Studies have indicated that a low long axis to short axis ratio of lymphadenopathy as measured by ultrasound can be a significant indicator of lymphoma and metastatic cancer as a cause of lymphadenopathy.
- MRI scanning: useful in the evaluation of thoracic, abdominal, and pelvic masses.
- PPD: can be used in the diagnosis of tuberculosis
- Tissue diagnosis of the node: this is done by incisional biopsy and remains the gold standard for diagnosis of lymphadenopathy.
Treatment
Treatment of lymphadenopathy is based on the etiology. Generally, treatment of lymphadenopathy is as follows:
- Infectious causes of lymphadenopathy can be treated with antibiotic therapy, antiviral therapy, or antifungal therapy.
- Immune therapy, systemic glucocorticoids can be used for autoimmune causes of lymphadenopathy
- For malignancies, any combination of surgery, chemotherapy, and radiation therapy can be used.
- If medication is the suspected cause, discontinue the medication if possible.
References
- ↑ Siddiqui S, Osher J (2017). "Assessment of Neck Lumps in Relation to Dentistry". Prim Dent J. 6 (3): 44–50. doi:10.1308/205016817821931079. PMID 30188316.
- ↑ Loizos A, Soteriades ES, Pieridou D, Koliou MG (2018). "Lymphadenitis by non-tuberculous mycobacteria in children". Pediatr Int. 60 (12): 1062–1067. doi:10.1111/ped.13708. PMID 30290041.
- ↑ Prudent E, La Scola B, Drancourt M, Angelakis E, Raoult D (2018). "Molecular strategy for the diagnosis of infectious lymphadenitis". Eur J Clin Microbiol Infect Dis. 37 (6): 1179–1186. doi:10.1007/s10096-018-3238-2. PMID 29594802.