Scrofula, or infectious cervical lymphadenitis, is a term predominantly applied to tuberculous and non-tuberculous mycobacterial infections (NTM) affecting the cervical lymph nodes. Mycobacterium are bacilli characterized microscopically by their dense lipid capsules that are “acid fast”, as they resist decoloration by acid alcohol after staining. This capsule protects the bacterial from lysis and promotes a strong cell-mediated response in the host. Humans are the only reservoir for M. tuberculosis. Other tuberculous bacilli that cause disease in humans are M. bovis, and M. africanum, which most often cause extrapulmonary disease. NTM are ubiquitous, and reside in the soil. They can be found in contaminated water, dairy products, eggs, dust, and even tap water. While mycobacterium tuberculosis is spread by airborne droplets that infect the host through the airways, NTM spread directly from the oral mucosal cavity. Approximately 95% of adult scrofula cases are caused by mycobacterium tuberculosis, while the remaining 5% are caused by NTM, such as M avium intracellulare, M scrofulaceum, M kansasii and M chelonei. In children, this statistic is reversed, with NTM responsible for up to 92% of scrofula cases.

Scrofula produces lymph nodes that are discrete, firm, and typically nontender, in contrast with the lymphadenopathy associated with acute infection that is often tender. A firm mass of matted nodes may become apparent with disease progression, and if untreated, lymphadenopathy can become fluctuant with draining fistulas. Enlarging nodes may compress the esophagus causing dysphagia. The presence of systemic symptoms is variable and more likely in immunocompromised patients.
Lymph nodes with centrally decreased density on CT are abnormal, reflecting either pathologic necrosis or tumor infiltration. Peripheral contrast enhancement reflects hyperemia of the inflamed lymph node capsule or increased lymph node vascularity. In general, inflammatory nodes have thick, irregular, enhancing margins, while metastatic nodes tend to have a thin rim of contrast enhancement.

Scrofula presents with a variable imaging appearance depending upon the stage of the disease. Tuberculous lymphadenitis may be unilateral or bilateral and is usually found in the internal jugular nodal chains (levels 2 - 4) and the spinal accessory chains (levels 5a and 5b). In the early infectious phase, non-necrotic nodes have homogeneous signal intensity and enhance homogeneously with contrast on both CT and MR. As the disease progresses, and nodes become necrotic, CT images demonstrate characteristic central low density, representing necrosis, with a thick rim of enhancement. On MR images, the necrotic center of the nodes will show intermediate signal intensity on T1-weighted images, low signal intensity on T2-weighted images, and will enhance with contrast. The surrounding granulation tissue, with its inflammatory hypervascularity and increased vascular permeability, will be markedly hyperintense on T2-weighted images. The nodes may become multiloculated and matted, simulating metastatic cervical disease both on imaging and clinically. Despite extensive necrosis, infiltration of adjacent fat planes is minimal that may help differentiate this process from other infections or malignant nodal disease. Chronic or post-treatment nodes are characterized by fibrous and calcific elements that are easily identified on CT. Calcification can also be seen in scrofula caused by NTM. On MR, treated nodes are homogeneously hypointense on both T1 and T2-weighted images and do not enhance with contrast.

The broad differential diagnosis of enhancing cervical lymphadenopathy in an adult includes, but is not limited to, metastatic squamous cell carcinoma, metastatic papillary thyroid carcinoma, lymphoma, tuberculous and nontuberculous mycobacterial lymphadenitis, cat-scratch disease, Kaposi’s sarcoma, AIDS-related lymphadenopathy, acute septic infection, Kimura’s disease, Castleman’s disease, and Kikuchi’s disease. Fungal infections and viral infections, such as Epstein-Barr virus, Herpes Simplex virus, Cytomegalovirus, and rubella also may present with bilateral diffuse lymphadenopathy.

Diagnosis usually requires fine needle aspiration (FNA) for histologic examination and culture. The sensitivity of FNA is 52.9% when used alone, but up to 82% when combined with PCR. The QuaniFERON-TB Gold serology test for M. tuberculosis is a new ELISA that detects the release of interferon gamma in the blood of sensitized individuals after incubation with mixtures of synthetic peptides that simulate M. tuberculosis proteins. Once Scrofula is diagnosed, it is important to determine the exact etiology, as tuberculous and NTM infections are treated differently. The current standard drug regimen for sensitive M. tuberculosis consists of isoniazid, rifampin, pyrzinamide, and ethambutol. for the first 2 months, followed by isoniazid and rifampin for a total of 6 -12 months. Lymphadenopathy may worsen during antituberculous therapy, representing an immune response to killed mycobacteria. Surgical intervention is reserved for complications such as abscess formation and draining sinuses. NTM infections can be addressed locally and are amenable to surgical intervention.