Causes of Lymphadenopathy in Childern

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Causes of peripheral lymphadenopathy in children

Last literature review version 18.3: Thu Sep 30 00:00:00 GMT 2010 | This topiclast updated: Thu Sep 30 00:00:00 GMT 2010

Official reprint from UpToDate® www.uptodate.com

©2011 UpToDate®

Authors Kenneth L McClain, MD, PhD Robert H Fletcher, MD, MSc

Section Editors Jan E Drutz, MD Sheldon L Kaplan, MD Donald H Mahoney, Jr, MD

Deputy Editor Mary M Torchia, MD

INTRODUCTION — The causes of peripheral lymphadenopathy in children will be reviewed

here. The approach to the child with peripheral lymphadenopathy, cervical lymphadenitis,

and the causes and evaluation of peripheral lymphadenopathy in adults are discussed

separately. (See "Etiology and clinical manifestations of cervical lymphadenitis in

children" and "Approach to the child with peripheral lymphadenopathy" and "Evaluation of

peripheral lymphadenopathy in adults".)

ANATOMY AND DEFINITIONS — The location of peripheral lymph node groups is shown

schematically in the figures (figure 1 and figure 2). Normal lymph nodes in most regions

usually are less than 1 cm in their longest diameter; normal lymph nodes in the

epitrochlear region usually are less than 0.5 cm in diameter, and normal lymph nodes in the

inguinal region usually are less than 1.5 cm in diameter. Normal lymph nodes tend to be

larger in childhood (ages 2 to 10 years) than later in life. Lymph nodes often are palpable in

the inguinal region in healthy individuals, perhaps because chronic trauma and infection are

so common in the lower extremities. Lymph nodes also may be palpable in the neck

(particularly submandibular lymph nodes) because of previous head and neck infections.

PATHOGENESIS — Lymph node enlargement may be caused by [1]:

Replication of cells within the node in response to antigenic stimuli or as a result of

malignant transformation

Entry of large numbers of cells exogenous to the node (eg, neutrophils or metastatic

neoplastic cells)

Deposition of foreign material within histiocytic cells of the node (as occurs in lipid

storage diseases)

Vascular engorgement and edema secondary to local cytokine release Suppuration secondary to tissue necrosis

EPIDEMIOLOGY — Children frequently have palpable lymph nodes because their immune

systems are being activated by environmental antigens and the common organisms to

which they are exposed. The prevalence of lymphadenopathy in the various lymph node

groups varies with age and site [2,3]. Small occipital and postauricular nodes, for example,

are common in infants, but not in older children [2]. In contrast, cervical and inguinal nodes

are more common after two years of age than in the first six months of life [2,3].

Epitrochlear and supraclavicular adenopathy are uncommon at any age.

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In one review, 44 percent of children younger than five years who were seen for well-child

visits and 64 percent of those seen for "sick" visits had lymphadenopathy [2]. Most of the

children with adenopathy detected at "sick" visits were between three and five years of age.

Many patients with unexplained lymphadenopathy (and their clinicians) are concerned

about the possibility of malignancy. The prevalence of malignancy among patients seen in

the primary care setting is relatively low [4,5]. In contrast, the prevalence of malignancy inlymph node biopsies performed in pediatric referral centers ranges from 13 to 27 percent

[3,6,7].

In the largest of these series, 239 children underwent peripheral lymph node biopsies for

evaluation of lymphadenopathy [3]. The following etiologies were noted:

Reactive hyperplasia of undetermined etiology — 52 percent

Granulomatous disease (eg, cat scratch disease, atypical mycobacteria,

mycobacterium tuberculosis, fungal infections, or Langerhans cell histiocytosis

(histiocytosis X)) — 32 percent

Neoplastic disease — 13 percent; among these two-thirds had Hodgkin disease

Chronic dermatopathic or bacterial infections — 3 percent

A higher incidence of cancer is expected in patients with certain clinical characteristics,

including weight loss (>10 percent of body weight), abnormal complete blood count (CBC)

or chest radiograph, generalized adenopathy without a clear etiology, fevers, and lack of

upper respiratory tract infection symptoms. We recommend immediate biopsy for patients

who have these findings. In conjunction with the other reasons for biopsy (weight loss,

abnormal CBC, etc), lymph node biopsy also may be indicated in children with persistently

elevated erythrocyte sedimentation rate (ESR) or rising ESR despite antibiotic therapy.

(See "Approach to the child with peripheral lymphadenopathy", section on 'Lymph node

biopsy'.)

OVERVIEW — Lymphadenopathy can be caused by a vast array of diseases (table 1) and

drugs (table 2) [8,9]. Some presentations suggest a specific disease process, whereas a

few diseases present predominantly with lymphadenopathy.

It is clinically useful to classify the causes of lymphadenopathy according to whether the

lymphadenopathy is localized (in only one region, such as the neck or axilla) (table 3) or

generalized (occurring in more than one noncontiguous region) (table 4A-B) [9].

Conditions that can mimic lymphadenopathy are discussed below. (See 'Mimics of

lymphadenopathy' below.)

LOCALIZED LYMPHADENOPATHY — Localized lymphadenopathy is present in only one

region, such as the neck or axilla.

Cervical — The anterior cervical lymph nodes are enlarged in a variety of infections of the

head and neck and in systemic infections such as toxoplasmosis, Epstein-Barr virus (EBV),

or cytomegalovirus (CMV) infection. Only one-quarter of patients with enlarged cervical

nodes have another serious disease, which most often is mycobacterial. Upper posterior

cervical lymphadenopathy rarely is associated with significant diseases in children [8,9].

In considering the causes of cervical lymphadenopathy, it is helpful to distinguish between

acute (develops over a few days) and subacute/chronic (develops over weeks to months)




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lymphadenopathy and whether the adenopathy is unilateral or bilateral. (See "Etiology and

clinical manifestations of cervical lymphadenitis in children".)

Inflamed cervical nodes that develop over a few days and progress to fluctuation, especially

in children, typically are caused by staphylococcal (picture 1) and streptococcal infection

[10]. The source of infection may be unapparent even after careful examination. Treatment

typically begins first with a course of antibiotics, but incision and drainage may be

indicated. Antimicrobial treatment of cervical lymphadenitis is discussed separately.(See "Diagnostic approach to and initial treatment of cervical lymphadenitis in children",

section on 'Initial treatment'.)

Fluctuant cervical nodes that develop over weeks to months without significant

inflammation or tenderness suggest infection with Mycobacterium tuberculosis, atypical

mycobacteria, or Bartonella henselae, the agent of cat scratch disease. Cat scratch disease

is discussed separately. (See "Microbiology, epidemiology, clinical manifestations, and

diagnosis of cat scratch disease".)

Mycobacterial infections can present with lymphadenopathy alone, especially in the neck

(scrofula). M. avium complex and M. scrofulaceum account for most cases in children

[11,12]. Nodes typically are nontender, enlarge over weeks to months without prominent

systemic symptoms, and can progress to matting and fluctuation (picture 2). (See "Etiology

and clinical manifestations of cervical lymphadenitis in children", section on 'NTM infection'.)

Hard nodes, often associated with cancer in adults, are found infrequently in children. The

nodes involved with Hodgkin disease are rubbery and difficult to differentiate from

hyperplastic nodes or nodes caused by granulomatous disease. (See "Overview of Hodgkin

lymphoma in children and adolescents".)

Less common causes of cervical adenopathy, which are discussed below, include

malignancy, Kawasaki disease, Langerhans cell histiocytosis, autoimmune

lymphoproliferative disease, Rosai-Dorfman disease, sarcoidosis, and Kikuchi disease.(See 'Uncommon but important causes' below and "Clinical manifestations and diagnosis of

Kawasaki disease" and "Langerhans cell histiocytosis, Juvenile xanthogranuloma, and

Erdheim-Chester disease".)

Supraclavicular — Supraclavicular (or lower cervical) (figure 1) lymphadenopathy is

associated with a high risk of malignancy (up to 75 percent) in children [7,9]. Right

supraclavicular adenopathy is associated with cancer of the mediastinal lymph nodes. Left

supraclavicular adenopathy ("Virchow's node") suggests intraabdominal malignancy, most

often lymphoma.

Axillary — The axillary nodes receive drainage from the arm, thoracic wall, and breast.

Infections, including cat scratch disease, are common causes of axillary lymphadenopathy.In one series of 31 children who underwent axillary node biopsies, 11 (35 percent) had

reactive hyperplasia, and five (16 percent) had cat scratch disease [3]. (See "Microbiology,

epidemiology, clinical manifestations, and diagnosis of cat scratch disease".)

Inguinal — Inguinal lymphadenopathy in children usually is not associated with a specific

etiology unless the nodes are very large (>3 cm).

Epitrochlear — Palpable epitrochlear nodes (figure 2) are often pathologic in children.

However, many biopsied nodes show only hyperplasia if they are associated with cuts or




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abrasions and there are no other signs suggestive of malignancy. The differential diagnosis

for epitrochlear lymphadenopathy includes infections of the forearm or hand, leukemia,

lymphoma, and atypical mycobacterial infections. (See "Overview of the presentation and

classification of acute lymphoblastic leukemia in children".)

GENERALIZED LYMPHADENOPATHY — Generalized lymphadenopathy is present in two

or more noncontiguous regions. It may be a feature of numerous systemic diseases, many

of which are recognized by other clinical findings (table 4A-B). Several of these diseases arediscussed below.

Systemic infection — Systemic bacterial or viral illnesses are the most common causes of

generalized adenopathy [12]. Common viral causes of generalized lymphadenopathy

include EBV or CMV mononucleosis, rubella, and measles (in parts of the world where

rubella and measles are endemic).

Mononucleosis — Classic infectious mononucleosis is characterized by the triad of

moderate to high fever, pharyngitis, and lymphadenopathy. A characteristic distribution of

lymph node involvement occurs; typically it is symmetric and involves the posterior cervical

more than the anterior cervical chain. The posterior cervical nodes are deep to the

sternocleidomastoid muscles (figure 1). Lymphadenopathy also may be present in the

axillary and inguinal areas, which helps to distinguish infectious mononucleosis from other

causes of pharyngitis. The lymph nodes are kidney-shaped and may be large.

Lymphadenopathy peaks in the first week and then gradually subsides over two to three

weeks. (See "Infectious mononucleosis in adults and adolescents".)

HIV — Lymphadenopathy is common in primary human immunodeficiency virus (HIV)

infection. Nontender adenopathy primarily involving the axillary, cervical, and occipital

nodes develops in the majority of individuals during the second week of acute symptomatic

HIV infection, concomitant with the emergence of a specific immune response to HIV [12].

The nodes decrease in size after the acute presentation, but a modest degree of

adenopathy tends to persist. (See "Natural history and classification of pediatric HIV

infection", section on 'Clinical manifestations'.)

Miliary tuberculosis — Miliary tuberculosis is an important consideration in patients

with generalized lymphadenopathy. Miliary tuberculosis can be mistaken for malignancy.

(See "Clinical manifestations; diagnosis; and treatment of miliary

tuberculosis" and "Pathogenesis and epidemiology of miliary tuberculosis".)

Systemic lupus erythematosus — Enlargement of lymph nodes occurs in approximately

50 percent of patients with systemic lupus erythematosus (SLE). The nodes typically are

soft; nontender; discrete; varying in size from 0.5 to several centimeters; and usually

detected in the cervical, axillary, and inguinal areas. Lymphadenopathy is noted more

frequently at the onset of disease or in association with an exacerbation. Lymph node

enlargement also can be caused by infection or a lymphoproliferative disease in SLE; when

infections are present, the enlarged nodes are more likely to be tender. (See "Hematologic

problems in children and adolescents with systemic lupus erythematosus".)

Medications — Numerous medications may cause serum sickness that is characterized by

fever, arthralgias, rash, and generalized lymphadenopathy (table 3). Phenytoin can cause

generalized lymphadenopathy in the absence of a serum sickness reaction. (See "Serum

sickness and serum sickness-like reactions" and "Pharmacology of antiepileptic drugs",




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section on 'Phenytoin' and "Drug eruptions", section on 'Hypersensitivity syndrome'.)

UNCOMMON BUT IMPORTANT CAUSES — Lymphadenopathy is a central feature of

numerous less common systemic diseases that are important to consider because they are

life-threatening or require specific treatment (table 1).

Malignancy — Neoplastic causes of lymphadenopathy include Hodgkin disease, non-

Hodgkin lymphoma, neuroblastoma, acute lymphocytic leukemia, acute myeloid leukemia,and rhabdomyosarcoma.

The prevalence of malignancy among patients seen in the primary care setting is relatively

low [4,5]. In contrast, the prevalence of malignancy in lymph node biopsies performed in

pediatric referral centers ranges from 13 to 27 percent [3,6,7]. (See 'Epidemiology' above.)

As discriminant features of malignancy versus other etiologies, fever, duration of

adenopathy, and tenderness are not particularly helpful.

However, a higher incidence of cancer is expected in patients with certain clinical

characteristics, including weight loss (>10 percent of body weight), abnormal CBC or chest

radiograph, generalized adenopathy without a clear etiology, fevers, and lack of upper

respiratory tract infection symptoms. We recommend immediate biopsy for patients who

have these findings. In conjunction with the other reasons for biopsy (weight loss,

abnormal CBC, etc.), lymph node biopsy also may be indicated in children with persistently

elevated ESR or rising ESR despite antibiotic therapy. (See "Approach to the child with

peripheral lymphadenopathy", section on 'Lymph node biopsy'.)

Kawasaki disease — Kawasaki disease, though an uncommon illness, is the most frequent

cause of childhood vasculitis. This syndrome is associated with fever, cervical

lymphadenopathy, and a variety of other manifestations, including conjunctivitis, mucositis,

rash, and coronary artery aneurysms. (See "Clinical manifestations and diagnosis of

Kawasaki disease".)

Tularemia — Patients with tularemia typically present with fever and a single

erythematous papulo-ulcerative lesion with a central eschar (picture 3) that is accompanied

by tender regional lymphadenopathy (picture 4). The majority of cases in the United States

occur in Arkansas, Missouri, and Oklahoma. Sources of infections in humans include vectors

(eg, ticks, biting flies, and mosquitoes), handling of infected animals (rodents and rabbits),

ingestion of inadequately cooked meat, drinking contaminated water, cat scratches or bites,

or splashing infected material into the eye or rubbing eyes with contaminated fingers.

(See "Microbiology, pathogenesis, and epidemiology of tularemia" and "Clinical

manifestations, diagnosis, and treatment of tularemia".)

Langerhans cell histiocytosis — Langerhans cell histiocytosis may present with unilateralor bilateral cervical lymph nodes. Sometimes there is massive enlargement similar to those

seen in Rosai-Dorfman disease. (See 'Rosai-Dorfman disease' below and "Langerhans cell

histiocytosis, Juvenile xanthogranuloma, and Erdheim-Chester disease".)

Hemophagocytic lymphohistiocytosis — Hemophagocytic lymphohistiocytosis patients

have diffuse adenopathy in one-third of cases. (See "Hemophagocytic lymphohistiocytosis".)

Chronic granulomatous disease — Chronic granulomatous disease (CGD) encompasses

a heterogeneous group of disorders characterized by genetic defects in the ability of




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phagocytes to generate reactive oxygen intermediates from molecular oxygen. These

defects manifest primarily as an immunodeficiency resulting in frequent, severe infections,

including pneumonia, abscesses, suppurative adenitis, osteomyelitis, bacteremia/fungemia,

and superficial skin infections (cellulitis/impetigo). (See "Primary disorders of phagocytic

function: An overview".)

Castleman's disease — Castleman's disease is an uncommon lymphoproliferative disorder

characterized by massive lymphadenopathy and systemic features such as fever,hepatomegaly, splenomegaly, and polyclonal hypergammaglobulinemia. (See "Castleman's

disease".)

Autoimmune lymphoproliferative disease — Patients with autoimmune

lymphoproliferative disease (ALPS), also known as the Canale-Smith syndrome or

autoimmunity/lymphoproliferation syndrome, usually present in the first year of life with

massive cervical adenopathy that may obscure the angle of the jaw [13]. Splenomegaly

also can occur. Frequent associations with autoimmune diseases, including hemolytic

anemia, neutropenia, immune thrombocytopenic purpura, glomerulonephritis, and Guillain-

Barré syndrome, have been reported. The syndrome appears to be caused by a defect in

lymphocyte apoptosis (programmed cell death). (See "Apoptosis and autoimmune disease",section on 'Autoimmune lymphoproliferative syndrome'.)

Rosai-Dorfman disease — Rosai-Dorfman disease (sinus histiocytosis with massive

lymphadenopathy) often presents in children with markedly enlarged, nontender cervical

adenopathy of massive proportions, similar to patients with ALPS [14-18]. However, other

nodal sites, including the mediastinum, retroperitoneal, axillary, and inguinal sites, also

may be involved. Other manifestations include involvement of the nasal cavity, salivary

gland tissue and other regions of the head and neck, lytic bone lesions, pulmonary nodules,

or rash. Patients often are febrile when massive lymphadenopathy is present. Laboratory

evaluations show leukocytosis, polyclonal hypergammaglobulinemia, a hypochromic or

normocytic anemia, and elevated ESR. Treatment is uncertain; spontaneous resolution isfrequently observed [19].

Kikuchi disease — Kikuchi disease is a rare, benign condition of unknown cause usually

characterized by cervical lymphadenopathy (although it may be more generalized) and

fever. It is discussed in detail separately. (See "Kikuchi's disease".)

Inflammatory pseudotumor — Inflammatory pseudotumor of lymph nodes is a syndrome

of lymphadenopathy in one or more node groups, often with systemic symptoms. Nodes

show a fibrosing and inflammatory process [20].

Churg-Strauss syndrome — Massive lymphadenopathy in children with asthma may be a

rare manifestation of the Churg-Strauss syndrome (asthma, tissue and peripheral blood

eosinophilia, and granulomatous vasculitis). A case report of a boy with this triad plus a

mediastinal mass suggesting Hodgkin disease has been reported [21]. (See "Epidemiology,

pathogenesis, and pathology of Churg-Strauss syndrome (allergic granulomatosis and

angiitis)".)

Sarcoidosis — Children with sarcoid may present with impressive cervical adenopathy,

similar to ALPS or Rosai-Dorfman disease patients. Lymphadenopathy is present in 50

percent of patients with sarcoidosis, who often have weight loss, cough, fatigue, lethargy,

bone and joint pain, anorexia, and headache [22]. African-Americans represent two-thirds




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to three-fourths of patients. (See "Clinical manifestations and diagnosis of sarcoidosis".)

MIMICS OF LYMPHADENOPATHY — Conditions that can mimic an enlarged lymph node

include [23-25]:

Infection or stones in any of the salivary glands

Congenital anomalies: branchial cleft cyst, cystic hygroma, thyroglossal duct cyst

Thyroid nodule Soft-tissue swelling from trauma or an insect bite or sting

Hematoma

Inguinal hernia

Hemangioma, lymphangioma

Lipoma

Dermoid

Rheumatoid nodules

SUMMARY

Normal lymph nodes in most regions usually are less than 1 cm in their longest

diameter; normal lymph nodes in the epitrochlear region usually are less than 0.5 cm,

and normal lymph nodes in the inguinal region usually are less than 1.5 cm.

(See 'Anatomy and definitions' above.)

Lymphadenopathy can be caused by a vast array of diseases and drugs (table 1). It is

clinically useful to classify the causes of lymphadenopathy according to whether the

lymphadenopathy is localized or generalized. (See 'Overview' above.)

Localized lymphadenopathy is present in only one region. Causes of localized

lymphadenopathy are listed in the table (table 2). (See 'Localized

lymphadenopathy' above.)

Generalized lymphadenopathy is present in two or more noncontiguous regions.

Causes of generalized lymphadenopathy are listed in the table (table 3).

(See 'Generalized lymphadenopathy' above.)

Uncommon but important causes of peripheral lymphadenopathy in children include

malignancy, Kawasaki disease, tularemia, Langerhans cell histiocytosis,

hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative disease, Rosai-

Dorfman disease, Kikuchi disease, inflammatory pseudotumor, and Churg-Strauss

syndrome. (See 'Uncommon but important causes' above.)

Malignancy should be considered in children with peripheral lymphadenopathy and

weight loss, abnormal complete blood count (CBC) or chest radiograph, generalizedadenopathy without a clear etiology, fever >1 week, and lack of upper respiratory

tract infection symptoms. Immediate biopsy is indicated in such children. In

conjunction with the other reasons for biopsy (weight loss, abnormal CBC, etc.),

lymph node biopsy also may be indicated in children with persistently elevated

erythrocyte sedimentation rate (ESR) or rising ESR despite antibiotic therapy.

(See 'Malignancy' above and "Approach to the child with peripheral

lymphadenopathy", section on 'Lymph node biopsy'.)




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REFERENCES

1. Jackson, MA, Chesney, PJ. Lymphatic system and generalized lymphadenopathy. In:

Principles and Practice of Pediatric Infectious Diseases, 2nd ed, Long, SS, Pickering,LK, Prober, CG (Eds), Churchill Livingstone, New York 2008. p.135.

2. Herzog, LW. Prevalence of lymphadenopathy of the head and neck in infants andchildren. Clin Pediatr (Phila) 1983; 22:485.

3. Knight, PJ, Mulne, AF, Vassy, LE. When is lymph node biopsy indicated in children withenlarged peripheral nodes? Pediatrics 1982; 69:391.

4. Ferrer, R. Lymphadenopathy: differential diagnosis and evaluation. Am Fam Physician1998; 58:1313.

5. HEINRICH, WA, JUDD ES, Jr. A critical analysis of biopsy of lymph nodes. Mayo ClinProc 1948; 23:465.

6. Lake, AM, Oski, FA. Peripheral lymphadenopathy in childhood. Ten-year experiencewith excisional biopsy. Am J Dis Child 1978; 132:357.

7. Soldes, OS, Younger, JG, Hirschl, RB. Predictors of malignancy in childhood peripherallymphadenopathy. J Pediatr Surg 1999; 34:1447.

8. Barton, LL, Feigin, RD. Childhood cervical lymphadenitis: a reappraisal. J Pediatr 1974;84:846.

9. Williamson HA, Jr. Lymphadenopathy in a family practice: a descriptive study of 249cases. J Fam Pract 1985; 20:449.

10. Lai, KK, Stottmeier, KD, Sherman, IH, McCabe, WR. Mycobacterial cervicallymphadenopathy. Relation of etiologic agents to age. JAMA 1984; 251:1286.

11. Spark, RP, Fried, ML, Bean, CK, et al. Nontuberculous mycobacterial adenitis of

childhood. The ten-year experience at a community hospital. Am J Dis Child 1988;142:106.

12. Gaines, H, von Sydow, M, Pehrson, PO, Lundbegh, P. Clinical picture of primary HIVinfection presenting as a glandular-fever-like illness. BMJ 1988; 297:1363.

13. Sneller, MC, Wang, J, Dale, JK, et al. Clincal, immunologic, and genetic features of anautoimmune lymphoproliferative syndrome associated with abnormal lymphocyteapoptosis. Blood 1997; 89:1341.

14. McAlister, WH, Herman, T, Dehner, LP. Sinus histiocytosis with massivelymphadenopathy (Rosai-Dorfman disease). Pediatr Radiol 1990; 20:425.

15. Horneff, G, Jürgens, H, Hort, W, et al. Sinus histiocytosis with massivelymphadenopathy (Rosai-Dorfman disease): response to methotrexate and

mercaptopurine. Med Pediatr Oncol 1996; 27:187. 16. Pulsoni, A, Anghel, G, Falcucci, P, et al. Treatment of sinus histiocytosis with massive

lymphadenopathy (Rosai-Dorfman disease): report of a case and literature review. AmJ Hematol 2002; 69:67.

17. Lee, KY, Yeon, YH, Lee, BC. Kikuchi-Fujimoto disease with prolonged fever in children.Pediatrics 2004; 114:e752.

18. La Barge DV, 3rd, Salzman, KL, Harnsberger, HR, et al. Sinus histiocytosis withmassive lymphadenopathy (Rosai-Dorfman disease): imaging manifestations in thehead and neck. AJR Am J Roentgenol 2008; 191:W299.




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19. Payne, JH, Evans, M, Gerrard, MP. Kikuchi-Fujimoto disease: a rare but importantcause of lymphadenopathy. Acta Paediatr 2003; 92:261.

20. Moran, CA, Suster, S, Abbondanzo, SL. Inflammatory pseudotumor of lymph nodes: astudy of 25 cases with emphasis on morphological heterogeneity. Hum Pathol 1997;28:332.

21. Casey, M, Radel, E, Ratech, H. Lymph node manifestations of limited Churg-Strausssyndrome. J Pediatr Hematol Oncol 2000; 22:468.

22. Pattishall, EN, Strope, GL, Spinola, SM, Denny, FW. Childhood sarcoidosis. J Pediatr1986; 108:169.

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25. Yaris, N, Cakir, M, Sözen, E, Cobanoglu, U. Analysis of children with peripherallymphadenopathy. Clin Pediatr (Phila) 2006; 45:544.




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GRAPHICS

Lymph nodes of the head and neck

This drawing schematically depicts the major lymph nodes in the head and neckarea that are likely to be enlarged on physical examination in patients withvarious local or systemic diseases. The major nodal groups are shown here inbold, with the areas draining into these nodal groups noted when appropriate.While enlargement of both the left and right supraclavicular lymph nodes mayreflect disease in the thorax, left supraclavicular nodal enlargement, because ofits drainage pattern, may also reflect the presence of abdominal involvement (ie,Virchow's node).




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Lymph node regions in the body




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Causes of peripheral lymphadenopathy

Cause Examples

Infections

Bacterial

Localized Streptococcal pharyngitis; skin infections; tularemia; plague; catscratch disease; diphtheria; chancroid; rat bite fever

Generalized Brucellosis; leptospirosis; lymphogranuloma venereum; typhoid fever

Viral Human immunodeficiency virus; Epstein-Barr virus; herpessimplex virus; cytomegalovirus; mumps; measles; rubella;hepatitis B; dengue fever

Mycobacterial Mycobacterium tuberculosis; atypical mycobacteria

Fungal Histoplasmosis; coccidioidomycosis; cryptococcosis

Protozoal Toxoplasmosis; Leishmaniasis

Spirochetal Secondary syphilis; Lyme disease

Cancer Squamous cell cancer head and neck; metastatic; lymphoma;leukemia

Lymphoproliferative Angioimmunoblastic lymphadenopathy with dysproteinemia

Autoimmune lymphoproliferative disease

Rosai-Dorfman disease

Hemophagocytic lymphohistiocytosis

Immunologic Serum sickness; drug reactions (phenytoin)

Endocrine Hypothyroidism; Addison's disease

Miscellaneous Sarcoidosis; lipid storage diseases; amyloidosis; histiocytosis;chronic granulomatous diseases; Castleman's disease; Kikuchi'sdisease; Kawasaki disease; inflammatory pseudotumor;systemic lupus erythematosus; rheumatoid arthritis; Still'sdisease; dermatomyositis; Churg-Strauss syndrome




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Drugs that cause lymphadenopathy

Data from Pangalis, GA, Vassilakopoulos, TP, Boussiotis, VA, Fessas, P, Semin Oncol 1993;

20:570.

Allopurinol

Atenolol

Captopril

Carbamazepine

Cephalosporins

Gold

Hydralazine

Penicillin

Phenytoin

Primidone

Pyrimethamine

Quinidine

Sulfonamides

Sulindac




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Causes of localized lymphadenopathy in children

Lymph nodegroup

Area ofdrainage

Causes

Occipital Posterior scalp, neck Common: Scalp infections (including tinea

capitis, lice), insect bites, seborrhea,roseola (human herpes virus 6, HHV6)

Less common: Rubella, acute lymphoblasticleukemia

Posterior auricular Temporal and parietalscalp

Rubella, roseola (HHV6, HHV7)

Anterior auricular(preauricular)

Anterior and temporalscalp, anterior earcanal and pinna,lateral conjunctivaand eyelids

Common: Eye or conjuctival infections (eg,adenovirus, oculoglandular syndrome)

Less common: Cat scratch disease,tularemia, listeriosis

Submental Central lower lip,floor of mouth

Tongue, gum, buccal mucosal, and dentalinfections (eg, gingivostomatitis), group Bstreptococcal infection (in infants


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Data from: Segal, GB, Hall, CB. Lymphadenopathy. In: Primary Pediatric Care, 4th ed, Hoekelman,

RA (Ed), Mosby, St. Louis 2001. p.1192. Perkins, SL, Segal, GH, Kjeldsberg, CR. Work-up of

lymphadenopathy in children. Semin Diagn Pathol 1995; 12:284. Malley, R. Lymphadenopathy. In:

Textbook of Pediatric Emergency Medicine, 5th ed, Fleisher, GR, Ludwig, S, Henretig, FM (Eds),

Lippincott Williams and Wilkins, Philadelphia 2006. p.421.

rat-bite fever, toxoplasmosis,rheumatologic disease of the hand or wrist

Epitrochlear Hand, forearm, elbow Common: Viral diseases, sarcoidosis,tularemia, infection of hands

Less common: Cat scratch disease,tularemia, secondary syphilis,

rheumatologic disease of the hand or wrist

Inguinal Leg and genitalia Common: Genital herpes, primary; syphilis,gonococcal infection, lymphoma

Less common: Yersinia pestis, chancroid,lymphogranuloma venereum

Popliteal Posterior leg andknee

Local infection




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Infectious causes of generalized lymphadenopathy in children

InfectiousSelected clinical features that may be

present

Viral

Epstein-Barr virus Tonsillopharyngitis, splenomegaly (>50 percent), fever,malaise, fatigue; periorbital edema

Cytomegalovirus Fever, malaise, fatigue, occasional hepatosplenomegaly

Herpes simplex virus Grouped vesicles; gingivostomatitis

Varicella zoster virus Generalized vesicular rash appearing in crops

Adenovirus Respiratory tract symptoms, pharyngitis, conjunctivitis

Rubella Fever and rash; may be asymptomatic

Hepatitis B virus High-risk sexual behavior, exposure to blood products

Rubeola (measles) Maculopapular rash with cranial to caudal progression

Humanimmunodeficiencyvirus

Recurrent bacterial infection, opportunistic infection, fever,diarrhea, encephalopathy, failure to thrive,hepatosplenomegaly

Fungal

Coccidioidomycosis(valley fever)

Pneumonia; travel to or residence in endemic area (eg,southwestern United States)

Blastomycosis Pneumonia; travel to or residence in an endemic area (eg,southeastern and south central United States, Africa)

Bacterial

Group A streptococcaldisease

Rash followed by desquamation

Brucellosis Fever, sweats, malaise, fatigue, weight loss, ingestion ofunpasteurized milk; exposure to cattle, sheep, or goats

Tularemia Fever, chills, headache; ingestion of undercooked meats,exposure to rabbits, rodents, biting flies, or mosquitoes

Leptospirosis Fever, rigors, myalgia, headache, conjunctival injection, rash,hepatosplenomegaly

Spirochetal

Syphilis Rash, fever, malaise, anorexia, and weight loss,heptaomegaly

Lyme disease Erythema migrans, fever, headache, myalgia, malaise,arthralgia

Parasitic

Toxoplasmosis Most infections in immunocompetent hosts areasymptomatic; myalgia, fatigue, fever, splenomegaly, andmaculopapular rash may be present; exposure to cats




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Data from: Malley, R. Lymphadenopathy. In: Textbook of Pediatric Emergency Medicine, 5th ed,

Fleisher, GR, Ludwig, S, Henretig, FM (Eds), Lippincott Williams and Wilkins, Philadelphia 2006.

p.421.

Leishmaniasis Cutaneous lesions, organomegaly, fever, cachexia; exposureto sandflies

Malaria Fever, travel to or residence in an endemic area




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Noninfectious causes of generalized lymphadenopathy in children

NeoplasticSelected clinical features that

may be present

Primary

Hodgkin lymphoma Usually manifests as cervicallymphadenopathy; adenopathy may beunilateral; respiratory distress can occur

Non-Hodgkin lymphoma Rapidly enlarging diffuse adenopathy,abdominal pain, vomiting; adenopathy isusually bilateral; respiratory distress canoccur

Metastatic

Acute lymphocytic or myelogenousleukemia

Ill appearance, bleeding,hepatosplenomegaly, anemia,thrombocytopenia; occipital nodes often

prominent

Neuroblastoma Abdominal mass; opsoclonus-myoclonus,proptosis, periorbital echymoses, nasalobstruction, Horner syndrome, subcutaneousnodules, secretory diarrhea

Rhabdomyosarcoma Proptosis; nasal, aural, or sinus obstruction;hematuria; urinary obstruction; constipation

Immunologic

Vasculitis syndromes (systemic lupuserythematosus, rheumatoid arthritis)

Patients may have generalized adenopathyduring the acute phase of illness

Serum sickness Rash, splenomegaly, myalgia, arthritis

Autoimmune hemolytic anemia Lymphadenopathy coincides with hemolysis

Chronic granulomatous disease Recurrent infection, skin abscesses,suppurative adenitis

Metabolic

Gaucher disease Hepatosplenomegaly, anemia,thrombocytopenia, osteopenia

Niemann-Pick disease Hepatosplenomegaly, loss of neurologicfunction

Drugs

Phenytoin, phenobarbitol,carbamazepinem, isoniazid, aspirin,barbiturates, penicillin, tetracycline,iodides, sulfonamides, allopurinol, andphenylbutazone.

Severe maculopapular rash, fever,hepatosplenomegaly, jaundice, anemia,leukopenia, and plasmacytosis occurringduring or after the lymphadenopathy

Miscellaneous

Sarcoidosis Multisystem granulomatous disease;generalized adenopathy with prominent




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Data from: Malley, R. Lymphadenopathy. In: Textbook of Pediatric Emergency Medicine, 5th ed,

Fleisher, GR, Ludwig, S, Henretig, FM (Eds), Lippincott Williams and Wilkins, Philadelphia 2006.

p.421.

cervical involvement

Hemophagocytic lymphohistiocytosis Fever, hepatosplenomegaly, neurologicsymptoms, rash

Castleman's disease Fever, hepatosplenomegaly, polyclonalhypergammaglobulinemia

Langerhans cell histiocytosis Rash (brown to purplish papules), mucosallesions, lytic bone lesions, proptosis, diabetesinsipidus

Rosai-Dorfman disease (sinushistiocytosis with massivelymphadenopathy)

Chronic bilateral cervical adenopathy ischaracteristic; other nodal groups areinvolved in most cases; fever, anemia,leukocytosis, elevated ESR, andhypergammaglobulinemia

Hyperthyroidism Tachycardia, hypertension, diaporesis, weightloss, goiter, hyperreflexia

Papular acrodermatitis (Gianotti-Crosti

syndrome)

Rash on face, buttocks, limbs, palms, and

soles; hepatomegaly




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Staphylococcus aureus adenitis

Acute unilateral cervical adenitis caused by S. aureus.Submandibular nodes are affected in more than 50 percent ofcases. The lymph node is usually 3 to 6 cm in diameter, tender,warm, erythematous, nondiscrete, and poorly mobile.




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Mycobacterium avium adenitis

Mycobacterium avium cervical lymphadenitis in the parotid andsubmandibular regions. The parotid node underwent incompleteexcision and began to relapse. The submandibular node beganto spontaneously drain and formed an overlying scab.




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Tularemia eschar

Courtesy of Todd M. Pollack, MD.




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Tularemia adenitis

Ulceroglandular tularemia involving the submental nodecharacterized by a papular lesion in the drainage field of theinflamed lymph node.



Causes of Lymphadenopathy in Childern

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