Chapter 484 Lymphadenopathy
Palpable lymph nodes are common in pediatrics. Lymph node enlargement is caused by proliferation of normal lymphoid elements or by infiltration with malignant or phagocytic cells. In most patients, a careful history and a complete physical examination suggest the proper diagnosis. A few key questions significantly aid in determining a diagnosis.
Is the mass a lymph node? Nonlymphoid masses (cervical rib, thyroglossal cyst, branchial cleft cyst or infected sinus, cystic hygroma, goiter, sternomastoid muscle tumor, thyroiditis, thyroid abscess, neurofibroma) occur frequently in the neck and less often in other areas. Is the node enlarged? Lymph nodes are not usually palpable in the newborn. With antigenic exposure, lymphoid tissue increases in volume. They are not considered enlarged until their diameter exceeds 1 cm for cervical and axillary nodes and 1.5 cm for inguinal nodes. Other lymph nodes usually are not palpable or visualized with plain radiographs. What are the characteristics of the node? Acutely infected nodes are usually tender. There may also be erythema and warmth of the overlying skin. Fluctuance suggests abscess formation. Tuberculous nodes may be matted. With chronic infection, many of these signs are not present. Tumor-bearing nodes are usually firm and nontender and may be matted or fixed to the skin or underlying structures.
Is the lymphadenopathy localized or generalized? Generalized adenopathy (enlargement of >2 noncontiguous node regions) is caused by systemic disease (Table 484-1) and is often accompanied by abnormal physical findings in other systems. In contrast, regional adenopathy is most frequently the result of infection in the involved node and/or its drainage area (Table 484-2). When due to infectious agents other than bacteria, adenopathy may be characterized by atypical anatomic areas, a prolonged course, a draining sinus, lack of prior pyogenic infection, and unusual clues in the history (cat scratches, tuberculosis exposure, venereal disease). A firm, fixed node should always raise the question of malignancy, regardless of the presence or absence of systemic symptoms or other abnormal physical findings.
Table 484-1 DIFFERENTIAL DIAGNOSIS OF SYSTEMIC GENERALIZED LYMPHADENOPATHY
| INFANT | CHILD | ADOLESCENT |
|---|---|---|
| COMMON CAUSES | ||
| Syphilis | Viral infection | Viral infection |
| Toxoplasmosis | EBV | EBV |
| CMV | CMV | CMV |
| HIV | HIV | HIV |
| Toxoplasmosis | Toxoplasmosis | |
| Syphilis | ||
| RARE CAUSES | ||
| Chagas disease (congenital) | Serum sickness | Serum sickness |
| Congenital leukemia | SLE, JRA | SLE, JRA |
| Congenital tuberculosis | Leukemia/lymphoma | Leukemia/lymphoma/Hodgkin disease |
| Reticuloendotheliosis | Tuberculosis | Lymphoproliferative disease |
| Lymphoproliferative disease | Measles | Tuberculosis |
| Metabolic storage disease | Sarcoidosis | Histoplasmosis |
| Histiocytic disorders | Fungal infection | Sarcoidosis |
| Plague | Fungal infection | |
| Langerhans cell histiocytosis | Plague | |
| Chronic granulomatous disease | Drug reaction | |
| Sinus histiocytosis | Castleman disease | |
| Drug reaction | ||
CMV, cytomegalovirus; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; JRA, juvenile rheumatoid arthritis (Still disease); SLE, systemic lupus erythematosus.
From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier, p 863.
Table 484-2 SITES OF LOCAL LYMPHADENOPATHY AND ASSOCIATED DISEASES
CERVICAL
ANTERIOR AURICULAR
SUPRACLAVICULAR
EPITROCHLEAR
INGUINAL
HILAR (NOT PALPABLE, FOUND ON CHEST RADIOGRAPH OR CT)
AXILLARY
ABDOMINAL
CMV, cytomegalovirus; CT, computed tomography; EBV, Epstein-Barr virus; HHV-6, human herpesvirus 6.
From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier, p 864.
Evaluation and treatment of lymphadenopathy is guided by the probable etiologic factor, as determined from the history and physical examination. Many patients with cervical adenopathy have a history compatible with viral infection and need no intervention. If bacterial infection is suspected, antibiotic treatment covering at least streptococci and staphylococci is indicated. Those who do not respond to oral antibiotics, as demonstrated by persistent swelling and fever, require IV antistaphylococcal antibiotics. If there is no response in 1-2 days or if there are signs of airway obstruction or significant toxicity, CT or ultrasound of the neck should be obtained. If pus is present, it may be aspirated, with CT or ultrasound guidance, or if it is extensive, may require incision and drainage. Gram stain and culture of the pus should be obtained. The sizes of involved nodes should be documented before treatment. Failure to decrease in size within 10-14 days also suggests the need for further evaluation, which may include a complete blood cell count with differential; Epstein-Barr virus, cytomegalovirus, Toxoplasma, and cat scratch disease titers; antistreptolysin O or anti-DNAse serologic tests; tuberculin skin test; and chest radiograph. If these studies are not diagnostic, consultation with an infectious disease or oncology specialist may be helpful. Biopsy should be considered if there is persistent or unexplained fever, weight loss, night sweats, supraclavicular location, mediastinal mass, hard nodes, or fixation of the nodes to surrounding tissues. Biopsy may also be indicated if there is an increase in size over baseline in 2 wk, no decrease in size in 4-6 wk, or no regression to “normal” in 8-12 wk, or if new signs and symptoms develop.
484.1 Kikuchi-Fujimoto Disease (Histiocytic Necrotizing Lymphadenitis)
Kikuchi-Fujimoto disease is a rare, usually self-limiting disease that was originally reported in patients of Asian heritage. Cases are now described in all ethnic groups. Familial cases have been reported. Presentation is varied and may include fever of unknown origin, but more often, it occurs in children 8-16 yr of age as unilateral posterior cervical adenitis, fever, malaise, elevated erythrocyte sedimentation rate, and leukopenia. Nodes range in size from 0.5-6.0 cm, are painful or tender in 50% of cases, may be multiple, and must be differentiated from lymphoma.
The etiology is unknown, although viral and bacterial causes have been suggested. Growing evidence supports an abnormal immune response as the cause. The diagnosis is made through lymph node biopsy. Histologic features include necrosis with karyorrhexis, a histiocytic infiltrate, crescentic plasmacytoid monocytes, and an absence of neutrophils. The disease usually spontaneously resolves within 6 mo, although relapses have occurred up to 16 yr later. Therapy with systemic steroids is reserved for cases with severe symptoms. Rarely, the disease has been fatal. Many autoimmune diseases have been associated with Kikuchi-Fujimoto disease, most commonly systemic lupus erythematosus.
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484.2 Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease)
This uncommon, benign, and usually self-limited disease has a worldwide distribution but is more common in Africa and the Caribbean. The etiology is unknown, but immune dysfunction is suspected. Patients present with massive symmetric, painless, cervical adenopathy, along with fever, leukocytosis, high erythrocyte sedimentation rate, and polyclonal elevation of immunoglobulin G. Night sweats and weight loss are frequently present. It rarely occurs at birth or in siblings, and males are affected more often than females.
Other nodal chains may be involved. Extranodal involvement occurs in approximately 40% of cases. Soft tissue involvement of all organ systems has been reported, but the most common sites include the skin, nasal cavity and sinuses, palate, orbit, bone, and central nervous system. Occasionally autoantibodies to erythrocytes or synovium may be present. A biopsy that demonstrates pale histiocytes containing engulfed lymphocytes (emperipolesis), in conjunction with expected clinical features, is diagnostic. The differential diagnosis includes Langerhans cell histiocytosis and lymphoma.
Therapy is usually not needed for this self-limited disease. However, the disease may recur frequently for many years. Life- or organ-threatening disease or exacerbations may respond to prednisone. Refractory cases have been treated with surgical excision or radiation. Rare patients have been treated with immune-modulating therapy, including interferon-α, 2-chlorodeoxyadenosine, imatinib, and rituximab. Therapy with antibiotics and chemotherapy has been unsuccessful.
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484.3 Castleman Disease
Castleman disease is an uncommon lymphoproliferative disease and is also called angiofollicular lymph node hyperplasia. The underlying etiology is unknown, although an association with human herpesvirus 8 has been identified. Human herpesvirus 8 may stimulate excessive production of interleukin 6 (IL-6). The disease usually presents in adolescents or young adults. Enlargement of a single node, most often in the mediastinum or abdomen, is the most common localized presentation. Some patients may have fever, night sweats, weight loss, and fatigue. Management includes surgery and/or radiation therapy.
Multicentric Castleman disease is a systemic disorder that causes lymphadenopathy, hepatosplenomegaly, fever, anemia, and polyclonal hypergammaglobulinemia. Multicentric Castleman disease may be associated with HIV infection, autoimmune disease–associated lymphadenopathy, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin lesions), and non-Hodgkin lymphoma. Non-Hodgkin lymphoma may be concurrent or may develop as a result of disease progression. There is no standard treatment for multicentric Castleman disease, but therapeutic options include chemotherapy, steroids, monoclonal antibodies to CD20 (rituximab), monoclonal antibodies to IL-6, anti-IL-6–receptor antibodies (tocilizumab), antiviral agents, and interferon-α. Chemotherapy regimens used for diffuse large B-cell lymphoma and/or rituximab are currently the most common frontline therapies and have achieved durable remissions. Ganciclovir is the most active antiviral agent. Steroids and anti-IL-6 therapies provide symptomatic relief, but symptoms return after stopping therapy.
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