Chapter 11. Lymphadenopathy PDF

Universidad Peruana de Ciencias Aplicadas Access Provided by: The Patient History: An Evidence­Based Approach to Differential Diagnosis, 2e Chapter 11. Lymphadenopathy Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD Case Scenario A 19­year­old man comes to your clin...

Universidad Peruana de Ciencias Aplicadas Access Provided by: The Patient History: An Evidence­Based Approach to Differential Diagnosis, 2e Chapter 11. Lymphadenopathy Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD Case Scenario A 19­year­old man comes to your clinic complaining of fever, headache, sore throat, and fatigue that started about 2 weeks ago. He has also noticed multiple swollen lymph glands in the front of his neck. He denies any rhinorrhea or cough. He is concerned because the lymph glands are sore to touch, and his symptoms are not improving. What additional questions are required to learn more about his swollen lymph glands? How would you classify his lymphadenopathy? What are the possible causes of enlarged lymph nodes? How does the interviewer establish a presumptive diagnosis using open­ended questions followed by more focused history taking? How do you distinguish benign causes of lymphadenopathy from more serious ones that require further evaluation? Introduction Lymphadenopathy is the enlargement of 1 or more lymph nodes. Patients may be alerted to the presence of enlarged lymph nodes by noticing visible nodular swelling, palpability, pain, or tenderness in 1 or more lymph node regions. It is normal to be able to palpate small lymph nodes in the neck and groin regions but generally not in the supraclavicular fossa, axilla, epitrochlear, or popliteal regions. Lymphadenopathy generally results from infiltration of lymph nodes by inflammatory or neoplastic cells, proliferation of resident lymphocytes, or expansion due to hemorrhage or abscess formation. In primary care settings, lymphadenopathy is rarely due to malignancy; upper respiratory tract infections or nonspecific conditions account for over two­thirds of cases. However, the risk of malignancy increases with age and other factors. Careful history taking is important in determining the cause of lymphadenopathy. Patients may be concerned or even anxious that lymphadenopathy may be a manifestation of cancer. The medical interview can assist in excluding malignancy or other serious underlying disease in most patients and inform subsequent evaluation for the remainder. Key Terms Lymphadenopathy1 Abnormal enlargement of 1 or more lymph nodes (> 1.0 cm in adults; > 1.5 cm in children and adolescents). Generalized lymphadenopathy2 Lymph node enlargement affecting multiple body regions. Localized lymphadenopathy2 Lymph node enlargement limited to a single body region (eg, cervical, inguinal). Etiology In primary care practice, more than two­thirds of patients with lymphadenopathy have nonspecific causes or upper respiratory illnesses (viral or 1–4 In one study, 84% of patients referred for evaluation of lymphadenopathy had a “benign” Downloaded Your IP is 52.36.32.128 bacterial), and2023­11­30 less than 1%10:38 have P a malignancy. Page 1 / 15 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, or PhD; Gina R.adenocarcinoma). Chacon, MD; Nephertiti Efeovbokhan, MD lymphadenopathy, diagnosis. The remaining 16% had a malignancy (lymphoma metastatic Of the patients with benign 63% had a ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility nonspecific or reactive etiology (no causative agent found), and the remainder had a specific cause demonstrated, most commonly infectious mononucleosis, toxoplasmosis, or tuberculosis. Thus, the vast majority of patients with lymphadenopathy will have a nonspecific etiology requiring Universidad Peruana de Ciencias Aplicadas Etiology Access Provided by: In primary care practice, more than two­thirds of patients with lymphadenopathy have nonspecific causes or upper respiratory illnesses (viral or bacterial), and less than 1% have a malignancy.1–4 In one study, 84% of patients referred for evaluation of lymphadenopathy had a “benign” diagnosis. The remaining 16% had a malignancy (lymphoma or metastatic adenocarcinoma). Of the patients with benign lymphadenopathy, 63% had a nonspecific or reactive etiology (no causative agent found), and the remainder had a specific cause demonstrated, most commonly infectious mononucleosis, toxoplasmosis, or tuberculosis. Thus, the vast majority of patients with lymphadenopathy will have a nonspecific etiology requiring few if any diagnostic tests.3 A comprehensive discussion of the myriad agents and diseases associated with lymphadenopathy is beyond the scope of this chapter but can be found elsewhere.3 The major causes of lymphadenopathy in the United States are listed below using the mnemonic CINEMA DIVITT (congenital, infectious, neoplastic, endocrine, metabolic, allergic, degenerative, inflammatory/immunologic, vascular, idiopathic or iatrogenic, traumatic, toxic). Another potentially useful framework for classifying and recalling the myriad causes of lymphadenopathy uses the mnemonic MIAMI (malignancies, infections, autoimmune disorders, miscellaneous and unusual conditions, and iatrogenic causes).4 Differential Diagnosis1,4 Prevalencea by Category in Primary Care1 ,4 • Congenital • Congenital syphilis Infectious5 18% (upper respiratory infections) • Bacteria —Actinomycosis —Atypical mycobacterial infections —Brucellosis —Cat­scratch disease (Bartonella henselae) —Chancroid —Chlamydia (lymphogranuloma venereum and trachoma) —Diphtheria —Leprosy —Lyme disease —Lymphogranuloma venereum —Plague —Primary and secondary syphilis —Scarlet fever Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. infection Lymphadenopathy, H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD —Skin (streptococci, Michael staphylococci) ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility —Streptococcal pharyngitis Page 2 / 15 —Plague Universidad Peruana de Ciencias Aplicadas Access Provided by: —Primary and secondary syphilis —Scarlet fever —Skin infection (streptococci, staphylococci) —Streptococcal pharyngitis —Tuberculosis (TB) —Tularemia —Dental pathology (periodontitis) • Viruses —Adenovirus —Cytomegalovirus (CMV) —Epidemic keratoconjunctivitis —Epstein­Barr virus (infectious mononucleosis) —Hepatitis B and C —Herpes simplex —Herpesvirus­6 —Herpesvirus­8 —Human immunodeficiency virus (HIV) —Measles (rubeola) —Rubella —Mumps —Vaccinia (smallpox vaccine) • Varicella­zoster virus (chickenpox) —Fungi —Coccidioidomycosis —Cryptococcosis —Histoplasmosis —Paracoccidioidomycosis —Sporotrichosis Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD • Parasites ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility —Chagas disease Page 3 / 15 —Histoplasmosis Universidad Peruana de Ciencias Aplicadas Access Provided by: —Paracoccidioidomycosis —Sporotrichosis • Parasites —Chagas disease —Filariasis —Kala­azar —Leishmaniasis —Toxoplasmosis —Trypanosomiasis • Rickettsiae —Q fever —Rickettsialpox —Scrub typhus • Mites — Scabies Neoplastic 0.8%–1.1% (4% if age > 40 years) • Lymphoma • Leukemia • Metastatic solid tumors (major primary sites): breast, colon, esophagus, head and neck, kidney, lung, ovary, prostate, skin (melanoma), stomach, testes Endocrine • Adrenal insufficiency • Hyperthyroidism • Hypothyroidism •Multiple endocrine neoplasia (see Neoplastic) Metabolic • Lipid storage diseases (Gaucher's, Niemann­Pick, Fabry's, Tangier's) • Severe hypertriglyceridemia Allergic2023­11­30 10:38 P Your IP is 52.36.32.128 Downloaded Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023• Serum McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility sickness Degenerative Page 4 / 15 Metabolic Universidad Peruana de Ciencias Aplicadas • Lipid storage diseases (Gaucher's, Niemann­Pick, Fabry's, Tangier's) Access Provided by: • Severe hypertriglyceridemia Allergic • Serum sickness Degenerative • Amyloidosis (secondary) Inflammatory/immunologic • Angioimmunoblastic lymphadenopathy • Amyloidosis (primary) • Dermatomyositis • Graft­versus­host disease • Juvenile rheumatoid arthritis • Mixed connective tissue disease • Primary biliary cirrhosis • Rheumatoid arthritis • Serum sickness • Silicone­associated • Systemic lupus erythematosus • Sarcoidosis • Sjögren's syndrome Vascular • Vasculitis • Churg­Strauss syndrome (adults) — Kawasaki's disease (children) Idiopathic or iatrogenic 29%–64% • Nonspecific lymphadenopathy • Prescribed medications (see Toxic) Traumatic 32% (including cuts and bites, in which secondary infection causes lymphadenopathy) Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 • Abrasions and lacerations Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility • Burns Page 5 / 15 • Prescribed medications (see Toxic) Universidad Peruana de Ciencias Aplicadas Access Provided by: Traumatic 32% (including cuts and bites, in which secondary infection causes lymphadenopathy) • Abrasions and lacerations • Burns • Cat­scratch disease (Bartonella henselae) • Operations Toxic (drugs, chemicals) • Antihypertensive medications —Atenolol —Captopril —Hydralazine • Antimicrobials —Cephalosporins —Penicillin —Pyrimethamine —Sulfonamides • Antiseizure medications —Carbamazepine —Phenytoin —Primidone • Antirheumatics —Allopurinol —Gold • Sulindac • Chemicals —Berylliosis —Silicosis aPrevalence estimate is unavailable when not indicated. Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility Getting Started with the History Page 6 / 15 Universidad Peruana de Ciencias Aplicadas —Silicosis Access Provided by: aPrevalence estimate is unavailable when not indicated. Getting Started with the History Before the visit, review the patient's problems and medications as well as his or her past, family, social, sexual, travel, and occupational history for relevant clues. Remember that the risk of malignancy increases with age, particularly after age 50. Review the anatomy of the lymphatic system and the tissues and organs that drain to each lymph node group.6 Open­Ended Questions Tips for Effective Interviewing Tell me about the lump(s) you are feeling. Establish a setting of comfort and trust. • Where do you feel it? Begin with open­ended questions before focusing. • What does it feel like? Cover all important question areas not otherwise mentioned by the patient (see mnemonic below: COLD RAP TAPE). • When did you first notice it? Character: What is it like? Onset: When did it start? • Does it seem to be changing with time? Location: Where do you notice it? Duration: How long does it last? Have you had any recent illnesses or other symptoms? Tell me about your work, hobbies, pets, and travels. Relieving factors: What makes it better? Aggravating factors: What makes it worse? Can you think of any exposures you may have had to infectious agents, Precipitating factors: What brings it on? chemicals, insects, or people who were ill? Therapy: What have you tried to make it better? Associated symptoms: Do you have any other symptoms along with this? Have you taken any medications lately? Past medical history: Have you ever had anything like this before? Emotional impact: What concerns do you have about this and how it may Tell me about your current or past use of tobacco and alcohol. affect your life? Have you or any member of your family ever had any type of cancer? Tell me about your sexual history. Interview Framework Establish the onset and course of lymph node enlargement. Determine the presence or absence of other symptoms and whether symptoms are localized or generalized. Ask about exposures related to work, home, hobbies, habits, pets, travel, sexual activity, and medications. Figure 11–1 Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility Page 7 / 15 Determine the presence or absence of other symptoms and whether symptoms are localized or generalized. Universidad Peruana de Ciencias Aplicadas Ask about exposures related to work, home, hobbies, habits, pets, travel, sexual activity, and medications. Access Provided by: Figure 11–1 Lymph nodes of the head and neck, and the regions that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66:2103–2110. Copyright © David Klemm. Figure 11–2 Axillary lymphatics and the structures that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66:2103–2110. Copyright © Christy Krames. Figure 11–3 Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility Page 8 / 15 Axillary lymphatics and the structures that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Universidad Peruana de Ciencias Aplicadas Am Fam Physician. 2002;66:2103–2110. Copyright © Christy Krames. Access Provided by: Figure 11–3 Inguinal lymphatics and the structures that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66:2103–2110. Copyright © Christy Krames. Identifying Alarm Symptoms Most cases of lymphadenopathy have a benign and self­limited infectious or inflammatory cause.7,8 However, lymphadenopathy can be due to local infections, for which antimicrobial therapy can be beneficial; potentially life threatening diseases, such as cancer4; systemic infection; and autoimmune connective tissue disease (CTD). Remembering these conditions and their associated alarm symptoms or features facilitates earlier diagnosis and initiation of therapy. Serious Diagnoses Relative Prevalence in Primary Care Settings Cancer 1%–4% Local infections for which antimicrobial therapy may be beneficial 10%–30% Systemic infection < 1% Severe autoimmune disease < 1% Alarm Symptoms Consider Persistence or growth over several weeks or months Cancer Systemic inflammation/infection Lymph node described as “hard” Metastatic cancer Right supraclavicular lymphadenopathy Metastatic cancer of mediastinum, esophagus, or thorax Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Left11. supraclavicular lymphadenopathy Metastatic cancer originating in thorax, abdomen, or9 / 15 Page Chapter Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibilitypelvis Axillary area without local trauma or infection Breast cancer Systemic infection < 1% Severe autoimmune disease < 1% Universidad Peruana de Ciencias Aplicadas Access Provided by: Alarm Symptoms Consider Persistence or growth over several weeks or months Cancer Systemic inflammation/infection Lymph node described as “hard” Metastatic cancer Right supraclavicular lymphadenopathy Metastatic cancer of mediastinum, esophagus, or thorax Left supraclavicular lymphadenopathy Metastatic cancer originating in thorax, abdomen, or pelvis Axillary area without local trauma or infection Breast cancer Other metastatic cancer Epitrochlear area without local trauma or infection Lymphoma Sarcoidosis Secondary syphilis Inguinal lymphadenopathy Sexually transmitted diseases Abdominal/pelvic malignancies Generalized lymphadenopathy HIV infection Tuberculosis Sarcoidosis Medications Cervical, axillary, and inguinal lymphadenopathy associated with photosensitive rash, oral ulcers, Systemic lupus erythematosus or arthralgia Constitutional symptoms (malaise, fatigue, fever, unintentional weight loss, night sweats) Lymphoma Metastatic cancer Autoimmune diseases Tuberculosis Systemic infection Medications Hoarseness, dysphagia, chronic cough, hemoptysis Metastatic cancer originating in the head and neck or lung Abdominal pain, hematochezia, melena, hematuria Cancer (gastrointestinal, genitourinary system) Enteric infections Focused Questions After listening to the patient's open­ended description of lymph node enlargement, proceed to focused questions to determine the most likely cause. It is particularly important to inquire about alarm symptoms because their presence greatly influences subsequent diagnostic decision making. Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Page 10 / 15 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility QUESTIONS THINK ABOUT… Universidad Peruana de Ciencias Aplicadas Focused Questions Access Provided by: After listening to the patient's open­ended description of lymph node enlargement, proceed to focused questions to determine the most likely cause. It is particularly important to inquire about alarm symptoms because their presence greatly influences subsequent diagnostic decision making. QUESTIONS THINK ABOUT… Do you have a history of cancer? Metastatic cancer Have you traveled recently? Infectious causes Do you have a family history of head and neck (including thyroid, parathyroid) cancer? Multiple endocrine neoplasia Do you drink alcohol or use tobacco? If so, how much? Cancer (head and neck, lung, gastrointestinal) Have you ever been exposed to radiation? Cancer Have you ever had a positive TB skin test? Have you been exposed to anyone with TB untreated TB? Have you been exposed to undercooked meats, cat feces, or unpasteurized goat's milk? Toxoplasmosis Have you been bitten or scratched by a cat or exposed to a cat with fleas? Cat­scratch disease (Bartonella henselae) Do you ever consume unpasteurized milk or cheese? Brucellosis Do you hunt, clean, or eat the meat from wild animals? Tularemia Do you cut or scratch yourself often? Repeated minor trauma Have you had a tick bite or traveled to an area where Lyme disease is endemic (eg, Lyme disease northeast United States)? Do you engage in unprotected sexual intercourse? HIV Have you ever used injection drugs? HIV Hepatitis B and C Syphilis Have you experienced fever, joint pain, or rash with recent medication use? Medication­associated serum sickness with lymphadenopathy Do you have a mole that has changed in pigmentation, size, or shape? Melanoma Do you have a mole that is bleeding or has become painful, tender, itchy or scaly? Have you ever pricked yourself with a thorn from a rose or were you cutting roses? Sporotrichosis Do you have blisters in your genital area? Genital herpes Do you have a painful blistering rash in a band­like distribution on one side of your body? Herpes zoster Quality Is the swollen gland: Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 • Painful or tender? Infection Efeovbokhan, MD Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility Inflammatory causes • Hard? Metastatic cancer Page 11 / 15 Do you have a painful blistering rash in a band­like distribution on one side of your body? Herpes zoster Universidad Peruana de Ciencias Aplicadas Access Provided by: Quality Is the swollen gland: • Painful or tender? Infection Inflammatory causes • Hard? Metastatic cancer • Draining? Bacterial, mycobacterial infections Time course Tell me how the lymph gland problem has changed over time. Has it: • Been present for over a month? Malignancy • Continued to increase in size? Malignancy • Followed use of a new medication? Medication Associated symptoms In addition to the lymph gland swelling, have you also had any: • Fevers, chills, or sweats Infections Lymphoma Hyperthyroidism • Skin rash, redness, bites, insect stings, cuts, or scrapes? Bacterial or viral infections Mite infestation Secondary syphilis • Sore throat or cold symptoms? Viral or streptococcal pharyngitis • Genital sores or discharge? Sexually transmitted diseases • Fatigue? Epstein­Barr virus Hepatitis B and C infection CMV Thyroid dysfunction Adrenal insufficiency • Unintentional weight loss? Malignancy HIV infection TB • Breast lumps or discharge? Breast cancer • Persistent cough, hoarseness, or coughing up blood? Head and neck cancer Lung cancer TB Sarcoidosis • Difficulty swallowing, abdominal pain, pencil­thin stools, blood in your stool, or pitch Gastrointestinal malignancy Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 black, tarry stool? Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023• Change McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility in a mole? Melanoma • Pain or nodule in a testicle? Testicular cancer Page 12 / 15 • Persistent cough, hoarseness, or coughing up blood? Head and neck cancer Lung cancer TB Universidad Peruana de Ciencias Aplicadas Access Provided by: Sarcoidosis • Difficulty swallowing, abdominal pain, pencil­thin stools, blood in your stool, or pitch Gastrointestinal malignancy black, tarry stool? • Change in a mole? Melanoma • Pain or nodule in a testicle? Testicular cancer Mumps • Blood in your urine? Prostate cancer Renal or bladder malignancy • Joint pain, mouth ulcers, rashes after sun exposure, dry mouth, or dry eyes? Autoimmune CTDs Medication­associated serum sickness Modifying symptoms Does anything seem to make the lymph gland swelling better or worse, such as: • Antibiotic use? Better: Infection Worse: Medication­associated lymphadenopathy • Aspirin, ibuprofen, naproxen, or other nonsteroidal anti­inflammatory drugs? Better: Inflammation Worse: Sulindac­induced Diagnostic Approach (Including Algorithm) The diagnostic algorithm for lymphadenopathy is shown in Figure 11–4. Figure 11–4 Diagnostic algorithm: Lymphadenopathy. STD, sexually transmitted disease; CTD, connective tissue disease; Hx, history; TB, tuberculosis; URI, upper respiratory infection; ENT, ear, nose, and throat. †Other alarm symptoms suggestive of malignancy include progressive lymph node enlargement over Downloaded 2023­11­30 P Your use, IP isconstitutional 52.36.32.128symptoms (malaise, fatigue, fever, unintentional weight loss, night sweats), hoarseness, weeks and months, alcohol10:38 and tobacco Page 13 / 15 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD;melena, Gina R. abdominal Chacon, MD; Nephertiti Efeovbokhan, MD adenopathy without dysphagia, chronic cough, hemoptysis, hematuria, hematochezia, pain, and axillary or epitrochlear local ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility trauma or infection. Universidad Peruana de Ciencias Aplicadas Access Provided by: Diagnostic algorithm: Lymphadenopathy. STD, sexually transmitted disease; CTD, connective tissue disease; Hx, history; TB, tuberculosis; URI, upper respiratory infection; ENT, ear, nose, and throat. †Other alarm symptoms suggestive of malignancy include progressive lymph node enlargement over weeks and months, alcohol and tobacco use, constitutional symptoms (malaise, fatigue, fever, unintentional weight loss, night sweats), hoarseness, dysphagia, chronic cough, hemoptysis, hematuria, hematochezia, melena, abdominal pain, and axillary or epitrochlear adenopathy without local trauma or infection. Caveats Remember that what a patient reports as lymph node swelling may actually be another condition (eg, lipoma, sebaceous cyst, abscess, thyroid nodule). Lymph node swelling suggestive of a benign, self­limited condition may nevertheless prompt a strongly negative emotional response in patients or family members concerned about the possibility of malignancy. Nonspecific lymphadenopathy that is persistent or progressive should prompt repeat evaluation, patient education, and continued shared decision making regarding work­up options and their relative risks, costs, and benefits. Prognosis The prognosis of lymphadenopathy in the majority of cases seen in primary care settings is excellent, justifying reassurance and observation when the cause appears to be benign or self­limited, particularly in younger patients.9 The prognosis of lymphadenopathy due to serious systemic infections (eg, HIV, syphilis, TB) or malignancies depends on a number of factors, including the timeliness of establishing the correct diagnosis, initiation of appropriate therapy, patient­specific immunologic and physiologic responsiveness, and the biologic characteristics of the organism or neoplasm. Case Scenario | Resolution A 19­year­old man comes to your clinic complaining of fever, headache, sore throat, and fatigue that started about 2 weeks ago. He has also noticed multiple swollen lymph glands in the front of his neck. He denies any rhinorrhea or cough. He is concerned because the lymph glands are sore to touch and his symptoms are not improving. Additional History The patient has also noticed chills, sweats, muscle aches, malaise, and mild left upper quadrant abdominal achiness and fullness. The swollen lymph glands in the front of his neck do not seem to have changed in size since he first noticed them. He does not take any medications. He started college about 3 months ago, and he is in a monogamous relationship with a female partner. He denies injection drug use or unprotected sexual intercourse. He looked in his own throat with a mirror and flashlight and did not notice any white spots or pus. He denies abnormal bruising or bleeding. Question: What Is the Most Likely Diagnosis? A. Human immunodeficiency virus (HIV) infection B. Infectious mononucleosis C. Lymphoma D. Streptococcal pharyngitis E. Leukemia Correct answer: B The patient has painful cervical lymphadenopathy in addition to systemic features. Infectious mononucleosis (IM) caused by Epstein­Barr virus (EBV) commonly occurs in young adults. About 95% of affected patients have lymphadenopathy affecting the posterior cervical nodes; in a few cases, lymphadenopathy may be generalized. The affected lymph nodes are frequently mobile, tender, and symmetrically enlarged. Constitutional symptoms such as fever, malaise, fatigue, and myalgias are also common. Symptomatic splenomegaly presenting as left upper quadrant abdominal discomfort and fullness may also be seen. Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Page 14 / 15 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD Lymphoma usually with painless lymphadenopathy and occurs in •older patients, although Hodgkin's lymphoma may also present in young ©2023 McGraw Hill.presents All Rights Reserved. Terms of Use • Privacy Policy Notice • Accessibility adulthood. In patients with HIV infection, lymphadenopathy is often generalized, and additional history may reveal high­risk behaviors like multiple sexual partners and use of intravenous drugs. In streptococcal pharyngitis, the pharynx commonly shows an exudate, which this patient did not see. Correct answer: B Universidad Peruana de Ciencias Aplicadas The patient has painful cervical lymphadenopathy in addition to systemic features. Infectious mononucleosis (IM) caused by Epstein­Barr virus (EBV) Access Provided by: commonly occurs in young adults. About 95% of affected patients have lymphadenopathy affecting the posterior cervical nodes; in a few cases, lymphadenopathy may be generalized. The affected lymph nodes are frequently mobile, tender, and symmetrically enlarged. Constitutional symptoms such as fever, malaise, fatigue, and myalgias are also common. Symptomatic splenomegaly presenting as left upper quadrant abdominal discomfort and fullness may also be seen. Lymphoma usually presents with painless lymphadenopathy and occurs in older patients, although Hodgkin's lymphoma may also present in young adulthood. In patients with HIV infection, lymphadenopathy is often generalized, and additional history may reveal high­risk behaviors like multiple sexual partners and use of intravenous drugs. In streptococcal pharyngitis, the pharynx commonly shows an exudate, which this patient did not see. Patients with leukemia often complain of swollen lymph nodes in more than one lymph node group and have prominent constitutional symptoms along with a higher likelihood of abnormal bruising or bleeding. References 1. Fletcher RH. Evaluation of peripheral lymphadenopathy in adults. In: Rose BD, ed. UpToDate. 17.3 ed., Vol. 2009. Philadelphia, PA: Wolters Kluwer, 2009. 2. Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc. 2000;75:723–732. [PubMed: 10907389] 3. Henry PH, Longo DL. Enlargement of lymph nodes and spleen. In: Braunwald E, ed. Harrison's Principles of Internal Medicine . 17th ed. New York, NY: The McGraw­Hill Companies, Inc., 2008. 4. Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician . 2002;66:2103–2110. [PubMed: 12484692] 5. Heitman B, Irizarry A. Infectious disease causes of lymphadenopathy: localized versus diffuse. Lippincotts Prim Care Pract. 1999;3:19–38. [PubMed: 10214200] 6. Ballas ZK. Biology of the immune system. In: Berkow R, ed. The Merck Manual of Medical Information –Home Edition Online. Vol. 2003. Whitehouse Station, NJ: Merck & Co., Inc., 2000. 7. Williamson HA Jr. Lymphadenopathy in a family practice: a descriptive study of 249 cases. J Fam Pract. 1985;20:449–452. [PubMed: 3989485] 8. Anthony PP, Knowles SA. Lymphadenopathy as a primary presenting sign: a clinicopathological study of 228 cases. Br J Surg. 1983;70:412–414. [PubMed: 6871622] 9. Slap GB, Connor JL, Wigton RS, Schwartz JS. Validation of a model to identify young patients for lymph node biopsy. JAMA. 1986;255:2768–2773. [PubMed: 3701990] Suggested Reading Ferrer R. Lymphadenopathy: differential diagnosis and evaluation. Am Fam Physician . 1998;58:1313–1320. [PubMed: 9803196] Hurt C, Tammaro D. Diagnostic evaluation of mononucleosis­like illnesses. Am J Med . 2007;120:911.e1–e8. [PubMed: 17904463] LeBlond RF, Brown DD, DeGowin RL. Non­regional systems and diseases. In: LeBlond RF, Brown DD, DeGowin RL, eds. DeGowin's Diagnostic Examination . 9th ed. New York, NY: McGraw­Hill, 2009. Naeimi M, Sharifi A, Erfanian Y, Velayati A, Izadian S, Golparvar S. Differential diagnosis of cervical malignant lymphadenopathy among Iranian patients. Saudi Med J . 2009;30:377–381. [PubMed: 19271066] Richner S, Laifer G. Peripheral lymphadenopathy in immunocompetent adults. Swiss Med Wkly . 2010;140:98–104. [PubMed: 20069473] Downloaded 2023­11­30 10:38 P Your IP is 52.36.32.128 Chapter 11. Lymphadenopathy, Michael H. Zaroukian, MD, PhD; Gina R. Chacon, MD; Nephertiti Efeovbokhan, MD ©2023 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility Page 15 / 15