Though common in rheumatology, lymphadenopathy may be ‘hallmark’ of serious, rare disease
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Key takeaways:
- Lymphadenopathy is frequently seen in the most common rheumatological conditions.
- Differential diagnosis must consider rare, life-threatening conditions, such as IgG4-RD and Castleman disease.
Although swollen lymph nodes are often common in rheumatology, they are also a “hallmark” of rare, life-threatening diseases, such as IgG4-related disease and Castleman disease, according to data published in Rheumatology.
“Lymphadenopathy is an extremely common occasional finding in rheumatic diseases,” Carlo Selmi, MD, PhD, head of rheumatology and clinical immunology at the Humanitas Research Hospital, in Milan, Italy, told Healio.
“Lymphadenopathy in the rheumatological practice may be the consequence of a primary immune activation and part of the natural history of the rheumatic disease, represent an infectious complication of immunosuppressive therapies, correlate to an unrelated immune process — ie, vaccination — or indicate a lymphoproliferative transformation or metastasis from distant solid cancers, requiring immediate management,” he added. “Careful evaluation and differential diagnosis are therefore of utmost importance when assessing lymphadenopathy in this setting.”
In a review, Selmi, alongside lead author Stefano Rodolfi, MD, and colleagues laid out what they described as a “pragmatic approach” to navigate the assessment of swollen lymph nodes in rheumatology practice.
A common presence
Lymph node enlargement is common in systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s disease — where it is associated with more severe disease activity — and sarcoidosis, where it is “present in almost 100% of cases,” Selmi said.
Lymphadenopathy often requires no specific therapy, as it follows the disease course and improves with usual treatment, but sometimes it calls for surgery, he added.
“In rare cases, especially in the context of IgG4-RD or Castleman disease, the lymphadenopathy is so pronounced that it can cause mass-effect, compressing surrounding structures and systemic symptoms,” Selmi said. “In these scenarios, surgical removal is indicated if feasible.”
In general, history assessment should focus on indicators of infection or malignancy, such as a wound or suspicious nodule, as well as contact with animals or undercooked food, the researchers wrote. As lymphadenopathy can also arise from serum sickness, obtaining an accurate drug history may also be helpful.
“Thorough clinical history and physical examination is frequently sufficient to assess the benign-nature lymphadenopathy by excluding the presence of some red flags related to malignancy or infection,” Selmi said. “However, some cases require additional investigations, such as imaging or histological analysis. When the latter needs to be sought, excising an entire lymph node is generally encouraged to allow the evaluation of the tissue architecture and rule out malignancies.”
‘A careful differential diagnosis’
According to Selmi and colleagues, a differential diagnosis of swollen lymph nodes must consider IgG4-related disease (IgG4-RD) and Castleman disease.
“Lymphadenopathy represents a hallmark manifestation of rare immunological diseases such as Castleman disease and IgG4-related disease that must be considered in the differential diagnosis because effective targeted treatments can now impact the prognosis of these conditions,” they wrote.
Lymphadenopathy has been found to indicate poor prognosis and higher relapse rate in IgG4-RD. The swelling is “frequently generalized” and most commonly seen in mediastinal, axillary, intra-abdominal, cervical and inguinal areas, the researchers wrote.
“Lymphadenopathy is frequently encountered in IgG4-RD, sometimes as the first manifestation of the disease, weeks to years before onset of extra-nodal disease,” Selmi said. “It is important to note that presence of extra-nodal disease is essential to formulate the diagnosis of IgG4-RD, hence the case of isolated lymphadenopathy with histological features resembling IgG4-RD should prompt close follow up of these patients, to monitor for early signs of extra-nodal involvement.”
Castleman disease features lymphadenopathy “by definition,” Selmi added, and comes in two types — unicentric, involving enlargement in a single region, and multicentric, involving multiple regions and systemic inflammation.
“In the case of unicentric CD, lymphadenopathy is often the only clinical manifestation, and requires surgical removal in case of mass-effect,” Selmi said. “In multicentric CD, especially its most aggressive variants, lymphadenopathy represents a marker of the rampant interleukin-6 inflammation, which is driving the severe disease manifestations. In fact, there is now an approved treatment based on IL-6 blocking with siltuximab (Sylvant, Janssen Biotech) for idiopathic multicentric CD.”
According to Selmi, that histological evaluation of lymph nodes in suspected igg4-RD and Castleman disease “should prompt close follow-up of these patients, to monitor for early signs of extra-nodal involvement.”
Overall, swelling of lymph nodes is “a frequent clinical finding in rheumatology practice,” Selmi and colleagues concluded.
“Since rheumatologic patients are at higher risk of infectious and neoplastic complications, a careful differential diagnosis is of the utmost importance,” they added.
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