Lymphadenopathy

Lymphadenopathy
Lymphadenopathy
ICD-10	I88, L04, R59.1
ICD-9	289.1-289.3, 683, 785.6
DiseasesDB	22225
MeSH	D008206

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Synonyms and keywords: Lymph nodes enlarged, enlarged lymph nodes, lymphadenitis, swollen/enlarged lymph nodes

Overview

Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". When the infection is of the lymph nodes themselves, it is called lymphadenitis, but when the infection is of the lymph channels, it is called lymphangitis.

Classification

Depending upon the involvement of the lymph nodes, lymphadenopathy is classified as 3 types.

• Localized lymphadenopathy : due to localized spot of infection e.g. an infected spot on the scalp will cause lymph nodes in the neck on that same side to swell up
• Generalized lymphadenopathy : due to generalized infection all over the body e.g. influenza
  • Persistent generalized lymphadenopathy (PGL) : persisting for a long time, possibly without an apparent cause
• Dermatopathic lymphadenopathy : lymphadenopathy associated with skin disease.Tangier disease (ABCA1 deficiency) may also cause this.

Pathophysiology

• If an infection remains untreated, the center of the node may become necrotic, resulting in the accumulation of fluid and debris within the structure. This is known as an abscess and feels a bit like a tensely filled balloon or grape (a.k.a. fluctuance). Knowledge of which nodes drain specific areas will help search efficiently. Following infection, lymph nodes occasionally remain permanently enlarged, though they should be non-tender, small (less the 1 cm), have a rubbery consistency. It is common, for example, to find small, palpable nodes in the submandibular/tonsilar region of otherwise healthy individuals. This likely represents sequelae of past pharyngitis or dental infections.

• Malignancies may also involve the lymph nodes, either primarily (e.g. lymphoma) or as a site of metastasis. In either case, these nodes are generally firm, non-tender, matted (i.e. stuck to each other), fixed (i.e. not freely mobile but rather stuck down to underlying tissue), and increase in size over time. The location of the lymph node may help to determine the site of malignancy. Diffuse, bilateral involvement suggests a systemic malignancy (e.g. lymphoma) while those limited to a specific anatomic region are more likely associated with a local problem. Enlargement of nodes located only on the right side of the neck in the anterior cervical chain, for example, would be consistent with a squamous cell carcinoma, frequently associated with an intra-oral primary cancer.
• Diffuse upper airway infections (e.g. mononucleosis), systemic infections (e.g. tuberculosis) and inflammatory processes (e.g. sarcoidosis) can also cause lymphadenopathy (i.e. lymph node enlargement). This can be either symmetric or asymmetric.

Patterns of Benign (Reactive) Lymphadenopathy

There are three distinct patterns of benign lymphadenopathy:

• Follicular hyperplasia. Seen in infections, autoimmune disorders, and nonspecific reactions.
• Paracortical hyperplasia. Seen in viral infections, skin diseases, and nonspecific reactions.
• Sinus histiocytosis. Seen in lymph nodes draining limbs, inflammatory lesions, and malignancies.

Causes

Common Causes

• Acute infections (e.g. bacterial, or viral)
• Chronic infections (e.g tuberculous lymphadenitis, cat-scratch disease). Infectious mononucleosis is an acute viral infection, the hallmark of which is marked enlargement of the cervical lymph nodes.
• Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy
• Hodgkin lymphoma, non-Hodgkin lymphoma, hairy cell leukemia, give lymphadenopathy in all or a few lymph nodes
• Metastasis
• Sarcoidosis
• Systemic lupus erythematosus (SLE)
• Rheumatoid arthritis
• AIDS - generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). "Lymphadenopathy syndrome" has been used to describe the first symptomatic stage of HIV progression, preceding AIDS-related complex and full-blown AIDS.

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	No underlying causes
Dermatologic	Erythroderma, Infantile papular acrodermatitis, Melanoma, Merkel cell carcinoma, Mycosis fungoides
Drug Side Effect	Allopurinol, Atenolol , Captopril, Carbamazepine , Cephalosporins, Gold, Hydralazine, Penicillin, Phenytoin, Phenytoin, Primidone, Pyrimethamine, Quinidine, Sulfonamides, Sulindac, Yaws
Ear Nose Throat	No underlying causes
Endocrine	Hyperthyroidism
Environmental	No underlying causes
Gastroenterologic	Hepatitis A, Hepatitis B, Mesenteric adenitis, Stomach cancer, Tang Hsi Ryu syndrome, Whipple's disease
Genetic	Familial alphalipoprotein deficiency, Familial hemophagocytic lymphohistiocytosis, Familial histiocytic reticulosis, X-linked agammaglobulinaemia, X-linked lymphoproliferative syndrome
Hematologic	Acute lymphoblastic leukemia, Acute lymphocytic leukemia, Adult T cell leukemia, Autoimmune lymphoproliferative syndrome type 1, Castleman's disease, Chronic lymphocytic leukemia, Cutaneous T cell lymphoma, Familial hemophagocytic lymphohistiocytosis, Familial histiocytic reticulosis, Faisalabad histiocytosis, Gamma heavy chain disease, Hairy cell leukaemia, Hemoblastosis, Hemophagocytic reticulosis, Histiocytosis X, Hodgkin's Lymphoma, Hyperimmunoglobulinemia D and periodic fever syndrome, Large granular lymphocyte leukemia, Leukemia, Lipogranulomatosis, Lymphangioma, Lymphoma, Macroglobulinemia, Myeloproliferative disorder, Non-Hodgkin's Lymphoma, Primary autoimmune haemolytic anaemia, Plasma cell leukemia, Reticuloendotheliosis, Sinus histiocytosis, Systemic mastocytosis, Waldenström macroglobulinaemia, X-linked agammaglobulinaemia, X-linked lymphoproliferative syndrome, WT limb blood syndrome
Iatrogenic	No underlying causes
Infectious Disease	Bacteria: Anthrax, Borrelia burgdorferi, Bortonneuse fever, Brucellosis, Cat scratch disease, Congenital tuberculosis, Erysipelas, Granuloma inguinale, Lepromatous leprosy, Listeriosis, Lymphogranuloma venereum, Mastitis, Moraxella catarrhalis, Mycobacterium avium-intracellulare, Mycobacterium chelonei, Pinta, Plague, Rat-bite fever, Rickettsiae, Scrub typhus, Sennetsu fever, Septicaemia, Spotted fevers, Streptococcal tonsillitis, Syphilis, Three-day fever, Tuberculosis, Tularemia, Typhus fever, Vincent's angina, Yersinia pestis Virus: AIDS, Cowpox, Coxsackie virus, Cytomegalovirus infection, Dengue, German Measles/Rubella, Hepatitis A, Hepatitis B, Herpes simplex, Infectious mononucleosis, Influenza, Lassa fever, Measles, Mumps, Smallpox, Varicella, Western equine encephalitis Fungal: Coccidioidomycosis, Blastomycosis, Histoplasmosis, Sporotrichosis Parasitic: African Sleeping sickness, Chagas' disease, Congenital Toxoplasmosis, Filaria, Lymphatic filariasis, Onchocerciasis, Opisthorchiasis, Paracoccidioidomycosis, Rhabditida Infections, Toxoplasmosis, Trypanosomiasis, Visceral leishmaniasis /Kala-azar, Wuchereria bancrofti
Musculoskeletal / Ortho	Juvenile chronic arthritis, WT limb blood syndrome
Neurologic	Tang Hsi Ryu syndrome
Nutritional / Metabolic	Apo A-I deficiency, Sphingomyelinase deficiency
Obstetric/Gynecologic	No underlying causes
Oncologic	Acute lymphoblastic leukemia, Acute lymphocytic leukemia, Adult T cell leukemia, Breast cancer, Colorectal cancer, Chronic lymphocytic leukemia, Hemangiopericytoma, Lip cancer, Malignant lymphoma, Melanoma, Metastasis, Non-Hodgkin's Lymphoma, Pancoast tumor, Pseudolymphoma, Rhabdomyosarcoma, Stomach cancer, Cutaneous T cell lymphoma, Hairy cell leukaemia, Hodgkin's Lymphoma, Large granular lymphocyte leukemia, Lymphoma, Plasma cell leukemia, Merkel cell carcinoma, Mycosis fungoides, WT limb blood syndrome
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	Extrinsic allergic alveolitis, Pneumoconiosis, Sarcoidosis
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	Angioimmunoblastic lymphadenopathy, Angioimmunoblastic with dysproteinemia lymphadenopathy, Autoimmune lymphoproliferative syndrome type 1, Caspase-8 deficiency, Chediak-Higashi syndrome, Churg-Strauss syndrome, Common Variable Immunodeficiency, Extrinsic allergic alveolitis, Griscelli disease, Primary autoimmune haemolytic anaemia, Rheumatoid arthritis, Serum sickness, Siccardi syndrome, Still's Disease, Systemic lupus erythematosus/SLE, Sarcoidosis
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Amyloidosis, Aphthous stomatitis, Bejel, Black widow spider envenomation, Cystic hygroma, Gingivostomatitis, Idiopathic, Radiotherapy, Snake bite (Viperidae), Spider bite, Vaccination

Causes in Alphabetical Order

Acute lymphoblastic leukemia Acute lymphocytic leukemia Adult T cell leukemia African Sleeping sickness AIDS Amyloidosis Angioimmunoblastic lymphadenopathy Angioimmunoblastic with dysproteinemia lymphadenopathy Anthrax Aphthous stomatitis Apo A-I deficiency Autoimmune lymphoproliferative syndrome type 1 Bejel Black widow spider envenomation Borrelia burgdorferi Boutonneuse fever Breast cancer Brucellosis Caspase-8 deficiency Castleman's disease Cat scratch disease Chagas' disease Chediak-Higashi syndrome Chronic lymphocytic leukemia Churg-Strauss syndrome Coccidioidomycosis Colorectal cancer Common Variable Immunodeficiency Congenital Toxoplasmosis Congenital tuberculosis Cowpox Coxsackie virus infections Cutaneous leishmaniasis Cutaneous T cell lymphoma Cystic hygroma Cytomegalovirus infection Dengue Drug reaction Erysipelas Erythroderma Extrinsic allergic alveolitis Faisalabad histiocytosis Familial alphalipoprotein deficiency Familial hemophagocytic lymphohistiocytosis Familial histiocytic reticulosis Filaria Fungal blastomycosis Gamma heavy chain disease German Measles Gingivostomatitis Granuloma inguinale Griscelli disease Hairy cell leukaemia

Hemangiopericytoma Hemoblastosis Hemophagocytic reticulosis Hepatitis A Hepatitis B Herpes simplex Histiocytosis X Histoplasmosis Hodgkin's Lymphoma Hyperimmunoglobulinemia D and periodic fever syndrome Hyperthyroidism Idiopathic Infantile papular acrodermatitis Infectious mononucleosis Influenza Juvenile chronic arthritis Large granular lymphocyte leukemia Lassa fever Leishmaniasis Lepromatous leprosy Leukemia Lip cancer Lipogranulomatosis Listeriosis Lymphangioma Lymphatic filariasis Lymphogranuloma venereum Lymphoma Macroglobulinemia Malignant lymphoma Metastasis Mastitis Measles Melanoma Merkel cell carcinoma Mesenteric adenitis Moraxella catarrhalis Mucocutaneous leishmaniasis Mumps Mycobacterium avium-intracellulare Mycobacterium chelonei Mycosis fungoides Myeloproliferative disorder Non-Hodgkin's Lymphoma Onchocerciasis Opisthorchiasis Pancoast tumor Paracoccidioidomycosis Penicillium marneffei Phenytoin Pinta Plague Plasma cell leukemia Pneumoconiosis

Autoimmune haemolytic anaemia Protozoa Pseudolymphoma Radiotherapy Rat-bite fever Reticuloendotheliosis Rhabditida Infections Rhabdomyosarcoma Rheumatoid arthritis Rickettsiae Rubella Sarcoidosis Scrub typhus Secondary syphilis Sennetsu fever Septicaemia Serum sickness Siccardi syndrome Sinus histiocytosis SLE Smallpox Snake bite (Viperidae) Sphingomyelinase deficiency Spider bite Sporotrichosis Spotted fevers Sexually transmitted diseases Still's Disease - Juvenile-Onset Stomach cancer Streptococcal tonsillitis Syphilis Systemic lupus erythematosus Systemic mastocytosis Tang Hsi Ryu syndrome Three-day fever Toxoplasmosis Trypanosomiasis Tuberculosis Tularemia Typhus fever Vaccination Varicella Vincent's angina Visceral leishmaniasis / Kala-azar Waldenström macroglobulinaemia Western equine encephalitis Whipple's disease WT limb blood syndrome Wuchereria bancrofti X-linked agammaglobulinaemia X-linked lymphoproliferative syndrome Yaws Yersinia pestis

Bihilar lymphadenopathy

The causes can divide into the four commonest:

• Tuberculosis
• Sarcoidosis
• Lymphoma
• Other malignancies

Less common causes include:

• Churg-Strauss syndrome
• Human Immunodeficiency Virus
• Extrinsic allergic alveolitis
• Pneumoconiosis

Epidemiology and Demogaphics

The estimated incidence of lymphadenopathy in children in the United States ranges from 35% - 45%.

It is more common in the pediatric population.

Race and gender have no predilection in lymphadenopathy incidence.

Natural History, Complications and Prognosis

Natural History

The natural course of lymphadenopathy depends on the underlying cause. Lymphadenopathy due to infectious causes subsides once the infection is controlled.

Complications

• Mediastinal lymphadenopathy causes pressure symptoms like:
  • Superior vena cava syndrome
  • Tracheal and bronchial obstruction
  • Dysphagia
  • Hemoptysis
• Uric acid nephropathy
• Hyperkalemia
• Hypercalcemia
• Hypocalcemia
• Hyperphosphatemia
• Renal failure

Prognosis

Prognosis of lymphadenopathy depends entirely on the underlying etiology. Cancerous causes of lymphadenopathy have a poor prognosis compared to the infectious causes.

Diagnosis

Symptoms

Lymphadenopathy can present as

• Lump in the neck (e.g in tumors, sarcoidosis).
• Red, tender skin over lymph node.
• Swollen, tender, or hard lymph nodes.

Physical Examination

The major lymph node groups are located along the anterior and posterior aspects of the neck and on the underside of the jaw. If the nodes are quite big, you may be able to see them bulging under the skin, particularly if the enlargement is asymmetric (i.e. it will be more obvious if one side is larger then the other). To palpate, use the pads of all four fingertips as these are the most sensitive parts of your hands. Examine both sides of the head simultaneously, walking your fingers down the area in question while applying steady, gentle pressure. The major groups of lymph nodes as well as the structures that they drain, are listed below. The description of drainage pathways are rough approximations as there is frequently a fair amount of variability and overlap.

Palpating Anterior Cervical Lymph Nodes

Nodes are generally examined in the following order:

1. Anterior Cervical (both superficial and deep): Nodes that lie both on top of and beneath the sternocleidomastoid muscles (SCM) on either side of the neck, from the angle of the jaw to the top of the clavicle. This muscle allows the head to turn to the right and left. The right SCM turns the head to the left and vice versa. They can be easily identified by asking the patient to turn their head into your hand while you provide resistance. Drainage: The internal structures of the throat as well as part of the posterior pharynx, tonsils, and thyroid gland.
2. Posterior Cervical: Extend in a line posterior to the SCMs but in front of the trapezius, from the level of the mastoid bone to the clavicle. Drainage: The skin on the back of the head. Also frequently enlarged during upper respiratory infections (e.g. mononucleosis).
3. Tonsillar: Located just below the angle of the mandible. Drainage: The tonsilar and posterior pharyngeal regions.
4. Sub-Mandibular: Along the underside of the jaw on either side. Drainage: The structures in the floor of the mouth.
5. Sub-Mental: Just below the chin. Drainage: The teeth and intra-oral cavity.
6. Supra-clavicular: In the hollow above the clavicle, just lateral to where it joins the sternum. Drainage: Part of the throacic cavity, abdomen.

A number of other lymph node groups exist. However, palpation of these areas is limited to those situations when a problem is identified in that specific region (e.g. the pre-auricular nodes, located in front of the ears, may become inflamed during infections of the external canal of the ear).

Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as lymphadenitis. Infected lymph nodes tend to be:

• Firm, tender, enlarged and warm. Inflammation can spread to the overlying skin, causing it to appear reddened.

Malignancies may also involve the lymph nodes, either primarily (e.g. lymphoma) or as a site of metastasis. In either case, these nodes are generally:

• Firm, non-tender, matted (i.e. stuck to each other), fixed (i.e. not freely mobile but rather stuck down to underlying tissue), and increase in size over time.

Case Studies in Physical Examination

(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA)

• 

  Cervical Adenopathy: Massive right side cervical adenopathy and facial assymetry due to metastatic, intraoral squamous cell cancer.

• 

  Cervical Adenopathy: Massive right side cervical adenopathy and facial assymetry due to metastatic, intraoral squamous cell cancer.

• 

  Cervical Adenopathy: Large right anterior cervical lymph node.

• 

  Cervical Adenopathy: Multiple right sided cervical lymph nodes.

Imaging

Chest X Ray

Bihilar lymphadenopathy is a radiographic term that describes the enlargement of mediastinal lymph nodes. It is easily and most commonly identified by a chest x-ray.

• 

  Sarcoidosis bilateral hilar lymphadenopathy, non-caseating granulomas

CT

CT scan of the chest showing lymphadenopathy in the mediastinum due to sarcoidosis.

Biopsy

The test is used to diagnose cancer or an infection:

• When the doctor feels swollen glands and they do not go away
• When lymph nodes are present on a CT or MRI scan
• For some patients with breast cancer or melanoma, to see if the cancer has spread (sentinel lymph node biopsy)

Micrograph of dermatopathic lymphadenopathy, a type of lymphadenopathy. H&E stain

References

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