Lymphadenopathy

Revision as of 15:48, 30 July 2012 by Raviteja Reddy Guddeti (talk | contribs) (/* Causes in Alphabetical OrderSailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016 Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massac...)
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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.

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.

Microscopic pathology

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

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[3] [4]


Bihilar lymphadenopathy

The causes can divide into the four commonest:

Less common causes include:

Differentiating from other diseases

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.

Risk factors

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

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)

Laboratory Findings

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.


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

References

  1. 1.0 1.1 Status and anamnesis, Anders Albinsson. Page 12
  2. Chris Jennings (1993). "Understanding and Preventing AIDS: A Book for Everyone".
  3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016
  4. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X
  5. Blum JA, Neumayr AL, Hatz CF (2012). "Human African trypanosomiasis in endemic populations and travellers". Eur. J. Clin. Microbiol. Infect. Dis. 31 (6): 905–13. doi:10.1007/s10096-011-1403-y. PMID 21901632. Unknown parameter |month= ignored (help)
  6. Beukes CA, Thiart J (2012). "The incidence of human herpes virus-8 expression in lymph node biopsies from human immunodeficiency virus-positive patients". Histopathology. doi:10.1111/j.1365-2559.2012.04291.x. PMID 22716315. Unknown parameter |month= ignored (help)
  7. Mitsuhashi K, Shiseki M, Ishiyama M; et al. (2011). "[Angioimmunoblastic T-cell lymphoma with marked polyclonal plasmacytosis in peripheral blood and bone marrow mimicking plasma cell leukemia]". Rinsho Ketsueki (in Japanese). 52 (7): 563–9. PMID 21821991. Unknown parameter |month= ignored (help)
  8. Simonelli S, Gianazza E, Mombelli G; et al. (2012). "Severe high-density lipoprotein deficiency associated with autoantibodies against lecithin:cholesterol acyltransferase in non-Hodgkin lymphoma". Arch. Intern. Med. 172 (2): 179–81. doi:10.1001/archinternmed.2011.661. PMID 22271127. Unknown parameter |month= ignored (help)
  9. Simesen de Bielke MG, Yancoski J, Rocco C; et al. (2012). "A Missense Mutation in the Extracellular Domain of Fas: The Most Common Change in Argentinean Patients with Autoimmune Lymphoproliferative Syndrome Represents a Founder Effect". J Clin Immunol. doi:10.1007/s10875-012-9731-y. PMID 22752343. Unknown parameter |month= ignored (help)
  10. Schleenvoigt BT, Keller P, Stallmach A, Pletz MW (2012). "[African tick bite fever--rickettsiosis after holiday in South Africa]". Dtsch. Med. Wochenschr. (in German). 137 (17): 891–3. doi:10.1055/s-0032-1304902. PMID 22511280. Unknown parameter |month= ignored (help)
  11. Roushan MR, Amiri MJ (2012). "Update on Childhood Brucellosis". Recent Pat Antiinfect Drug Discov. PMID 22812616. Unknown parameter |month= ignored (help)
  12. Dispenzieri A, Armitage JO, Loe MJ; et al. (2012). "The clinical spectrum of Castleman's disease". Am J Hematol. doi:10.1002/ajh.23291. PMID 22791417. Unknown parameter |month= ignored (help)
  13. Chondrogiannis K, Vezakis A, Derpapas M, Melemeni A, Fragulidis G (2012). "Seronegative cat-scratch disease diagnosed by PCR detection of Bartonella henselae DNA in lymph node samples". Braz J Infect Dis. 16 (1): 96–9. PMID 22358366.
  14. http://picasaweb.google.com/mcmumbi/USMLEIIImages


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