Analysis of patients with lymphedema confirmed by lymphoscintigraphy (n = 90 total; 84 with stage/severity data) showed that Stemmer sign outcome (positive or negative) was not associated with lymphedema type (59 primary and 31 secondary), location (leg 75 and arm 15), severity (mild 34, moderate 20, and severe 30), or lymphoscintigram result (delayed transit 80 and dermal backflow 40); P = 0.06–0.50. Patients with stage 1 lymphedema (n = 14) were more likely to have a false-negative Stemmer sign compared to individuals with stage 2 (n = 56; P = 0.01) or stage 3 (n = 14; P = 0.04) disease.
One fourth of patients referred to a Lymphedema Program with “lymphedema” do not have the condition.7,8 “Lymphedema” often is used as a generic term to describe limb overgrowth regardless of the underlying etiology. Lymphedema usually can be diagnosed based on the patient’s medical history and physical examination. The Stemmer sign was originally described to differentiate lower extremity lymphedema from other causes of swelling.1,9 Stemmer correlated the inability to pinch the skin over the proximal second or third toe with patients who also exhibited abnormal resorption and backflow after the injection of patent blue dye.1
Lymphedema generally affects the distal extremity and the senior author has used the Stemmer sign to help differentiate lymphedema from other conditions affecting not only the lower limb, but also the upper extremity. Although Stemmer described pinching the dorsal skin over the proximal phalanx of the second toe, the senior author pinches the skin immediately proximal to the metatarsophalangeal joint because it is technically easier to perform, especially in the pediatric population. In addition, the senior author also translates the test to the upper extremity pinching the skin proximal to the metacarpalphalangeal joint of the index finger. The skin is pinched between the examiner’s index finger and thumb, rather than using a forceps, to reduce the risk of pain and skin injury. The upper extremity test is performed with the patient sitting up and their hands resting on their proximal thighs, whereas the lower extremity is examined while the patient is standing.
False-negative and false-positive findings have been observed by the senior author when compared with the patient’s medical history and lymphoscintigram findings. False-negative exams have been reported in the literature as well.10 We aimed to determine the accuracy of the Stemmer sign for lymphedema to determine if the test should continue to be used in clinical practice. The pathophysiology that prevents the pinching of the dorsal skin of the extremity in patients with lymphedema likely is thickened skin and excess subcutaneous fibroadipose tissue with edema. Lymphedema results in the accumulation of high-protein fluid in the subcutaneous tissues. This fluid causes inflammation, adipose deposition, and fibrosis.11–13 In contrast, other causes of swelling or limb overgrowth do not result in enough inflammatory fibroadipose formation to prevent the pinching of the dorsal skin of the hand or foot: for example, venous stasis, heart disease, liver failure, renal insufficiency, rheumatologic disease, lipedema, hemihypertrophy, posttraumatic swelling, and vascular anomalies.
BMI was associated with both false-negative and false-positive Stemmer signs. Patients with lymphedema and a normal or below normal BMI could exhibit minimal swelling and a normal sign, whereas obese patients without lymphedema could have a positive sign. Obesity negatively affects lymphatic function by causing inflammation, fibrosis, and destruction of lymphatics.14–16 Consequently, normal weighted individuals would have less inflammation of their distal extremity causing skin thickening, fibrosis, and edema. Obese patients with greater subcutaneous adipose, in contrast, would be more likely to have inflammation, edema, and thicker skin/subcutis leading to a positive sign.
Our results show that the Stemmer sign has a sensitivity of 92% to predict lymphedema in patients who have the disease and a specificity of 57% to exclude lymphedema in patients who do not have the condition. Thus, we conclude that the test is a useful component of the physical examination in patients with suspected lymphedema. It is easy to perform and adds minimal effort when also evaluating the patient for pitting edema. Subjects with a positive finding are likely to have lymphedema, although obese individuals can exhibit the sign and have normal lymphatic function. A negative Stemmer sign does not rule out lymphedema, typically in patients with a normal BMI and stage 1 disease.
Although the Stemmer sign is a useful method to differentiate lymphedema from other diseases, we obtain a lymphoscintigram on almost all patients, because the test is more sensitive and specific for the condition. Lymphoscintigraphy is the most accurate method to determine whether a patient has lymphedema if the diagnosis is equivocal. The test also rules out the condition if the clinical suspicion is low, which provides comfort to the patient. We also typically perform the study for patients with a high clinical suspicion of lymphedema because it confirms the diagnosis, provides objective measurement of lymphatic dysfunction, and serves as a baseline evaluation to be compared to if the test is repeated in the future.
The authors would like to thank Steven J. Staffa, MS for his statistical expertise.
1. Stemmer R. A clinical symptom for the early and differential diagnosis of lymphedema. Vasa. 1976;5:261–262.
2. Fries R. Differential diagnosis of leg edema. MMW Fortschr Med. 2004;146:39–41.
3. Gloviczki P, Calcagno D, Schirger A, et al. Noninvasive evaluation of the swollen extremity: experiences with 190 lymphoscintigraphic examinations. J Vasc Surg. 1989;9:683–689; discussion 690.
4. Szuba A, Shin WS, Strauss HW, et al. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44:43–57.
5. Hassanein AH, Maclellan RA, Grant FD, et al. Diagnostic accuracy of lymphoscintigraphy for lymphedema and analysis of false-negative tests. Plast Reconstr Surg Glob Open. 2017;5:e1396.
6. Executive Committee. The diagnosis and treatment of peripheral lymphedema: 2016 Consensus document of the International Society of Lymphology. Lymphology. 2016;49:170–184.
7. Schook CC, Mulliken JB, Fishman SJ, et al. Differential diagnosis of lower extremity enlargement in pediatric patients referred with a diagnosis of lymphedema. Plast Reconstr Surg. 2011;127:1571–1581.
8. Maclellan RA, Couto RA, Sullivan JE, et al. Management of primary and secondary lymphedema: analysis of 225 referrals to a center. Ann Plast Surg. 2015;75:197–200.
9. Stemmer RA. Stemmer’s sign: possibilities and limits of clinical diagnosis of lymphedema [in German]. Wien Med Wochenschr. 1999;149:85–86.
10. Földi M, Földi E, Strößenreuther C. Földi’s Textbook of Lymphology: for Physicians and Lymphedema Therapists. 2012.München, Germany: Urban & Fischer.
11. Brorson H, Ohlin K, Olsson G, et al. Adipose tissue dominates chronic arm lymphedema following breast cancer: an analysis using volume rendered CT images. Lymphat Res Biol. 2006;4:199–210.
12. Ghanta S, Cuzzone DA, Torrisi JS, et al. Regulation of inflammation and fibrosis by macrophages in lymphedema. Am J Physiol Heart Circ Physiol. 2015;308:H1065–H1077.
13. Ly CL, Kataru RP, Mehrara BJ. Inflammatory manifestations of lymphedema. Int J Mol Sci. 2017;18:171.
14. Greene AK, Grant FD, Slavin SA. Lower-extremity lymphedema and elevated body-mass index. N Engl J Med. 2012;366:2136–2137.
15. Weitman ES, Aschen SZ, Farias-Eisner G, et al. Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes. PLoS One. 2013;8:e70703.
Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.
16. Savetsky IL, Torrisi JS, Cuzzone DA, et al. Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema. Am J Physiol Heart Circ Physiol. 2014;307:H165–H172.