Dr. Dorneanu presented the interesting case of a female in her mid50s who presented to the ED with fever and diarrhea after a recent admission on the ENT service with cervical lymphadenopathy. She was found to have Kikuchi-Fujimoto Disease also known as Kikuchi histiocytic necrotizing lymphadenitis or Kikuchi Disease.
What is Kikuchi-Fujimoto Disease?
This is a rare, self-limiting, benign condition of unknown cause usually characterized by cervical lymphadenopathy and fever. It was classically described in young females, but it is also seen more often in Black males. Patients present with enlarged nodes (range from 0.5-6.0) which are painful in about half of patients as well as fever, malaise, elevated ESR, and leukopenia.
Symptoms can also include a rash. Transient skin rashes similar to rubella or drug-induced eruptions may be seen in sicker patients. Some reports describe skin manifestations in up to 40 percent of patients: these ranged from facial erythema to erythematous macules, patches, papules, or plaques. Patients can also have arthritis, fatigue, or hepatosplenomegaly.
The pathogenesis is unknown. This is likely an immune response of T cells and histiocytes to an infectious agent, such as EBV or HHV6.
No effective treatment has been established for Kikuchi disease. Signs and symptoms usually resolve within one to four months
What is lymphadenopathy?
Lymphadenopathy is defined as an abnormal enlargement of a lymph node. Specifically, this counts as the following:
An inguinal node larger than 1.5 cm
An epitrochlear node larger than 0.5 cm
Any other node larger than 1 cm
What causes lymphadenopathy?
There are three general mechanisms to lymphadenopathy:
Proliferation in response to regional or systemic antigen
Metastatic invasion
Primary neoplastic transformation of the node itself
You can use the mnemonic "MIAMI" to help you remember the general causes of lymphadenopathy:
Malignancies
Infections
Autoimmune disease
Miscellaneous/zebras
Iatrogenic
How do I approach the patient presenting with lymphadenopathy?
Start with a good history and physical as always.
Ask about:
1. Age
79% of biopsies performed on patients less than 30 years old were benign
60% of biopsies performed on those over 50 were malignant
Age is single most predictive factor in determining whether lymphadenopathy is benign or malignant
2. Presence of infectious symptoms?
3. Presence of malignant symptoms (including classic B symptoms)?
Malignancy is increasingly likely with increasing age and increasingly likely with increasing duration.
If it’s less than 2 weeks or more than one year with NO change in size, it is unlikely to be malignant. Exceptions here are low-grade Hodgkin’s and NHL and occasionally CLL.
4. Epidemiologic clues?
Exposure to pets
Occupational exposures
Recent travel
High-risk behaviors
5. Medication Use- The following medications can cause lymphadenopathy: allopurinol, atenolol, captopril, carbamazepine, gold, hydralazine, penicillin, phenytoin, primidone, pyrimethamine, quinidine, bactrim, sulindac
6. Duration of lymphadenopathy: >4 weeks is chronic, needs workup
When doing your examination, concentrate on size, mobility, characteristics of notes and distribution. Make sure to examine ALL nodes (in a prior study, generalized lymphadenopathy was missed in 83% of patients). Remember: supraclavicular LAD has highest risk of malignancy (There is a 90% risk of malignancy in patients over age 40; this risk is still 25% if you are under 40.)
You may have previously learned node "characteristics" in medical school. Overall, the presence/absence of tenderness really means nothing, but the following can be helpful:
Stony hard nodes? Worry about metastatic spread
Very firm, rubbery nodes? Concerning for lymphoma
Suppurant node? Think abscess
"Shotty" nodes? Common in kids with viral illnesses
What do I do if my history and physical are not diagnostic or suggestive of an etiology?
Consider if your lymphadenopathy is generalized versus localized. Localized lymphadenopathy can give you an important clue to etiology: for instance, Kikuchi's is classically cervical lymphadenopathy.
If a benign etiology is suspected, just observe but careful follow-up (2 week intervals) is smart. Watch for rapid growth, spread, or any of the symptoms mentioned above
Otherwise, lab tests should be tailored towards what you think the etiology is. This could include:
CBC (make sure to get a manual differential)
throat culture, Monospot test
HIV testing
Hepatitis serologies
PPD or Quantiferon
CXR
Additionally, imaging has the benefit of being fairly accurate at differentiating benign from malignant lymphadenopathy. CT and MRI both have pretty good accuracy (65–90%) in the diagnosis of metastases to cervical lymph nodes.
When do I get a biopsy?
Based on prior studies, you can consider a biopsy if any of the following are present:
Age >40 years
Supraclavicular lymph node
Hard texture
Lack of pain or tenderness
Don’t biopsy if all of the following are present:
Node size < 1.0
<40 years old
Non-hard Lymph Node
Tender or painful
Biopsies are also considered in patients who have had chronic (more than four weeks) of lymphadenopathy.
References
Evaluation of lymphadenopathy. BMJ Best Practice. 2014.
Bazemore A, Smucker D. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2103-2110.
Ferrer R. Lymphadenopathy: Differential diagnosis and evaluation. Am Fam Physician. 1998;58(6):1313-1320.
Hines CM, Toy EC, Baker III B. The clinical evaluation of lymphadenopathy. Prim Care Update Ob Gyns. 2001;8(6):209-217. doi: http://dx.doi.org/10.1016/S1068-607X(01)00084-1.
Karnath B. Approach to the patient with lymphadenopathy. Hospital Physician. 2005:29-33.
Stutchfield CJ, Tyrrell J. Evaluation of lymphadenopathy in children. Paediatrics and Child Health. 2012;22(3):98-102. doi: http://dx.doi.org/10.1016/j.paed.2011.09.003.
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