In patients with generalized lymphadenopathy, the physical examination should focus on searching for signs of systemic illness. The most helpful findings are rash, mucous membrane lesions, hepatomegaly, splenomegaly or arthritis Table 4. Splenomegaly and lymphadenopathy occur concurrently in many conditions, including mononucleosis-type syndromes, lymphocytic leukemia, lymphoma and sarcoidosis.
Laboratory tests that may be useful in confirming the cause of lymphadenopathy are listed in Table 4. The presence of certain characteristic clinical syndromes may help the physician determine a suspected cause of lymphadenopathy.
Patients with these syndromes present with lymphadenopathy, fatigue, malaise, fever and an increased atypical lymphocyte count. Mononucleosis is most commonly due to Epstein-Barr virus infection.
The presence of the typical syndrome and positive results on a heterophilic antibody test Monospot test confirms the diagnosis. The most common cause of heterophil-negative mononucleosis is early Epstein-Barr virus infection. False-negative results on heterophilic antibody tests are especially common in patients younger than four years of age. Epstein-Barr virus infection may be confirmed by repeating the Monospot test in seven to 10 days.
Rarely is it necessary to confirm the diagnosis with IgM viral capsid antigen or early antigen antibody titers. If Epstein-Barr virus antibodies are absent, other causes of the mononucleosis syndrome should be considered.
These include toxoplasmosis, cytomegalovirus infection, streptococcal pharyngitis, hepatitis B infection and acute human immunodeficiency virus HIV infection. Acute infections with cytomegalovirus and Toxoplasma may be identified with IgM serology for those organisms. This syndrome is defined by the presence of a skin lesion with associated regional lymphadenopathy. The classic cause is tularemia, acquired by contact with an infected rabbit or tick; more common causes include streptococcal infection e.
This syndrome involves the combination of conjunctivitis and associated preauricular nodes. Common causes include viral kerato-conjunctivitis and cat-scratch disease resulting from an ocular lesion. Enlargement of the lymph nodes that persists for at least three months in at least two extrainguinal sites is defined as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection.
Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi's sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma. The decision will depend primarily on the clinical setting as determined by the patient's age, the duration of the lymphadenopathy and the characteristics and location of the nodes.
Because generalized lymphadenopathy almost always indicates that a significant systemic disease is present, the clinician should consider the diseases listed in Table 4 and proceed with specific testing as indicated. If a diagnosis cannot be made, the clinician should obtain a biopsy of the node. The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and most abnormal node which is not necessarily the most accessible node.
If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia. If the lymphadenopathy is localized, the decision about when to biopsy is more difficult. Patients with a benign clinical history, an unremarkable physical examination and no constitutional symptoms should be reexamined in three to four weeks to see if the lymph nodes have regressed or disappeared. Patients with unexplained localized lymphadenopathy who have constitutional symptoms or signs, risk factors for malignancy or lymphadenopathy that persists for three to four weeks should undergo a biopsy.
Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy. Many patients worry about the cause of their abnormal lymph nodes. To adequately address their fears, the physician should ask the patient about his or her concerns and respond to questions about specific diagnoses.
When biopsy is deferred, the physician should explain to the patient the rationale for waiting. Patients should be cautioned to remain alert for the reappearance of the nodes because lymphomatous nodes have been known to temporarily regress.
In most patients, lymphadenopathy has a readily diagnosable infectious cause. A diagnosis of less obvious causes can often be made after considering the patient's age, the duration of the lymphadenopathy and whether localizing signs or symptoms, constitutional signs or epidemiologic clues are present.
When the cause of the lymphadenopathy remains unexplained, a three- to four-week observation period is appropriate when the clinical setting indicates a high probability of benign disease. Already a member or subscriber?
Log in. Interested in AAFP membership? Learn more. Address correspondence to Robert Ferrer, M. Reprints are not available from the author. Lymphadenopathy in a family practice.
Lymphadenopathy in a family practice: a descriptive study of cases. J Fam Pract ;— Primary care medicine: office evaluation and management of the adult patient. Philadelphia: Lippincott, J Fam Pract. Williamson HA Jr. Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians' workup.
Lymph node biopsy for diagnosis: a statistical study. J Surg Oncol. Bennett JC, Plum F, eds. Cecil textbook of medicine. Philadelphia: Saunders, Libman H. Generalized lymphadenopathy. J Gen Intern Med.
Morland B. Arch Dis Child. Ability of primary care physicians to recognize physical findings associated with HIV infection. Semin Oncol. When to perform biopsies of enlarged peripheral lymph nodes in young patients. Sapira JD. The art and science of bedside diagnosis. Guest editors of the series are David A. Katerndahl, M. This content is owned by the AAFP.
A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv aafp. Want to use this article elsewhere? Get Permissions. Read the Issue. Recently found more above my collar bone and sides of neck and behind ear.
All pea sized, soft and very moveable. I feel so worried about all of this and can only think the worse all information I can find points to cancer. I also have developed a strange bony lump on my foot and recently hip pain.. I have another appointment with my eye dr this week.
Goodluck with your ultrasound appointment I hope you can find some answers. I am new to this site, I have a large firm lymph node in my submandibular gland, I am waiting for a urgent 2 week referral to ENT, the doctor felt it and said it was 2cm, What bothers me is that I have for the last 2 years been suffering with what I was told was oral lichen planus, which was diagnosed privately through Bupa, the consultant just looked in my mouth and said you have OLP, originally this was constant stinging and burning sensation, I have had no biopsy done, I am now getting paranoid that I have been misdiagnosed and that I have actually got oral cancer, I have made numerous visits to the dentist in this time but he has admitted that he does not know much about OLP.
Since I found the lump a week ago I have been going online and researchig large nodes in submandibular glands and it has stated that it is most likely a spread from oral cancer of either tongue floor of mouth or buccal mucosa, these are the areas where I was supposed to have OLP, I have not been able to go to work and I can not sleep at nights through the wworry my family are fed up with listening to my concerns.
I have pain in my neck and throat along with ear pain, and my mouth is very dry and sore. Hi sorry so late at posting again I didn't think anyone would've text me on this lol , the doctor that day said she couldn't feel the one which I think is around 2cm , she kept trying but couldn't feel it which was very frustrating because I know it's deffinatley there and but the other ones she could feel she said felt normal, I also discussed with her my health anxiety and she referred me for CBT which I haven't had yet I just hope when I do it's going to help with this horrendous anxiety, still got all the same nodes now , haven't changed in size I don't think but still worry me daily.
I hope you can get some answers as to why yours are swollen, keep us updated and I wish you all the best! Have you told your doctors that one of your lymph nodes have grown? Thanks for your reply! I have yet another appointment for an ultrasound on Thursday I will let you know how the ultrasound goes on Thursday and I wish you all the very best.
My MRI was last year in September which did show the lymph node was enlarged 1. Have a great evening and will chat soon! I hope you are feeling ok! I am having very similar symtons to you and just wondered how you got on? I have a lesion on my left eye that I am waiting for a biopsy for.
The function of the lymph node is to evaluate and when possible, process and initiate the immune response to the presented antigens. Lymph nodes can be thought of like a mesh of reticular cells containing lobules wherein the antigens are presented to the immune system.
Lobules anatomically contain 3 discreet compartments cortex, paracortex, and medulla in which B-cells, T-cells, and macrophages are separately sequestered. The appropriate cell line responds to the presented antigen by increasing its numbers. Commonly the cell lines can multiply by 3 to 5 times in 6 to 24 hours. The reticular network can stretch to contain the cell-swollen lobules. This increases the size of the lymph node and causes the clinical phenomenon of lymphadenopathy.
Lymph nodules are integrated with afferent and efferent blood vessels which allow a rich interface between intravascular and extravascular spaces. Macroscopically, the result is antigenic "policing" of both intravascular and interstitial fluids and ready immune response to threats. Microscopically, the decentralized hubs of antigen presentation and response allow for prompt action with an economy of lymphoid resources.
A history and physical examination are the cornerstones of time and cost-effective diagnosis of adenopathy. The obvious presence of strep pharyngitis and its related localized anterior cervical adenopathy requires far less clinical brainpower than generalized adenopathy secondary to sarcoidosis or a Gaucher disease.
The history itself involves gathering 5 important components: chronicity, localization, concomitant symptoms, patient epidemiology, and pharmacological exposure. The physical examination can be quite revealing especially with the location of the adenopathy and consideration of the lymphatic drainage of the related areas.
Once the determination has been made that the lymphadenopathy is either localized or general, strict attention to the localized area must be paid. For example:. Tuberculosis is among the leading cause of both regional and generalized adenopathy in the non-industrialized world. The differential diagnosis of the etiology of lymphadenopathy can be thought of in the following algorithm:After a thorough history and physical examination, lymphadenopathy can be initially categorized as:.
Unexplained localized lymphadenopathy after careful review of the history and epidemiology is further divided into patterns at no risk for malignancy or serious 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 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. 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 at the illness. If the results of the testing are still not clear, proceed onto 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.
The prognosis of lymphadenopathy, whether localized or generalized, is entirely dependent on the etiology of the enlarged lymph nodes. Most adenopathy in the general medicine office is caused by a treatable bacterial or treatable viral illness. However, HIV, active tuberculosis, and neoplasm all have more guarded prognoses. Generalities include the majority of localized lymphadenopathy has a better prognosis than the majority of generalized lymphadenopathy secondary to etiologies.
Etiologies that are established earlier in a clinical setting will tend to have better prognoses than those established later. Patient education plays a significant role in the deterrence of the processes that can cause pathological lymphadenopathy.
Most supraclavicular lymphadenopathies are associated with malignancy. The most powerful tool in the diagnosis of lymphadenopathy is a careful history and physical examination. The gold standard for diagnosis of lymphadenopathy is tissue obtained either by fine-needle aspiration or excisional biopsy. All generalized lymphadenopathy needs to be carefully worked up and the diagnosis established. The primary physician, physician assistant, and nurse practitioner can diagnose a significant number of the causes of lymphadenopathy after a careful workup.
However, when the diagnosis is in question varied, consultants can be utilized to clarify the situation to provide the best outcomes. The Korean journal of internal medicine. Journal of stomatology, oral and maxillofacial surgery. Fajgenbaum DC, Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease.
Surgical infections. Primary dental journal. Pediatrics international : official journal of the Japan Pediatric Society. Continuing Education Activity Lymphadenopathy is a common abnormal finding during the course of the physical exam in general medical practice.
Introduction Lymphadenopathy is a common abnormal finding during the course of the physical exam in general medical practice. If the patient is at no risk for malignancy or serious illness, the reasonable course of action is to observe the patient for 3 to 4 weeks to see if the lymphadenopathy resolves or improves. In which case, the clinician is safely cleared to follow the patient.
If the lymphadenopathy does not resolve or improve, the next step is to obtain a biopsy. If the patient is judged to have a risk for malignancy or serious illness, the procedure is to proceed immediately to biopsy. For unexplained generalized lymphadenopathy, the key to diagnosis is a history to evaluate for suspected causes. The initial search would be questioning for a mononucleosis-type syndrome such as evidenced by fever atypical lymphocytosis and malaise included in these differentials would be Epstein-Barr virus, cytomegalovirus, toxoplasmosis, and especially in the case of a flu-like illness and her rash the initial stages of an HIV infection.
The second step in the evaluation of unexplained generalized lymphadenopathy involves a careful review of epidemiological cues. Bacterial etiologies of lymphadenopathy include Staphylococcus , Streptococcus , Salmonella , Syphilis , and Yersinia Mycobacterial etiology of lymphadenopathy include tuberculosis and Mycobacterium avium intracellulare MAI Fungal etiology of lymphadenopathy include coccidioidomycosis, histoplasmosis, and Candida Parasitic etiology of lymphadenopathy include toxoplasmosis, Chagas, and many of the ectoparasites Neoplastic causes of lymphadenopathy include both primary malignancies and metastatic malignancies: Acute lymphoblastic leukemia ALL , Hodgkin lymphoma, non-Hodgkin lymphoma, neuroblastoma, pediatric acute myelocytic leukemia, rhabdomyosarcoma, metastatic carcinoma of the lung, metastatic carcinoma of the viscera of the gastrointestinal GI tract, metastatic breast cancer, and metastatic thyroid cancer and metastatic renal cancer.
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