AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: John E McClay, MD, Assistant Professor, Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Medical Center, University of Texas Southwestern Medical School
John E McClay is a member of the following medical societies: American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, and American Medical Association
Coauthor(s):
Michael R Lewis, MD, Staff Physician, Department of Otolaryngology, University of Texas Southwestern Medical Center
Editors: Lanny Garth Close, MD, Chair, Professor, Department of Otolaryngology-Head and Neck Surgery, Columbia University College of Physicians and Surgeons; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Peter S Roland, MD, Professor, Department of Neurological Surgery, Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, Director of Clinical Center for Auditory, Vestibular and Facial Nerve Disorders, Chief of Pediatric Otology, University of Texas Southwestern Medical Center; Adjunct Professor of Communicative Disorders, School of Human Development, Chief of Medical Services at Callier Center for Communicative Disorders, University of Texas at Dallas; Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders; Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
scrofula, tuberculosis, TB, cervical tuberculosis, cervical tuberculous lymphadenopathy, mycobacterial lymphadenitis, extrapulmonary tuberculosis
Background
Tuberculosis (TB) is the oldest documented infectious disease. In the United States, pulmonary TB accounts for most TB cases. Scrofula is the Latin word for brood sow, and it is the term applied to TB of the neck. Cervical TB is usually a result of an infection in the lymph nodes, known as lymphadenitis. Extrapulmonary TB, such as scrofula, is observed most often in individuals who are immunocompromised, who account for up to 50% of these cervical infections.
Scrofula has been known to afflict people since antiquity, and during the Middle Ages, the king's touch was thought to be curative. In modern times, surgery has played a pivotal role in the diagnosis and treatment of scrofula. Over the past several decades, however, surgical intervention has played a decreasing role because it has been fraught with persistent disease and complications. As in pulmonary TB, antituberculous chemotherapy has become the standard of care for scrofula, and newer diagnostic techniques (eg, fine-needle aspiration) have replaced more invasive methods of tissue harvesting.
Today, approximately 95% of mycobacterial cervical infections in adults are caused by Mycobacterium tuberculosis and the rest are caused by atypical mycobacterium or nontuberculous mycobacterium (NTM). In children, this trend is reversed, with 92% of cases due to atypical mycobacterium. NTM was first recognized as a cause of cervical adenitis in 1956. More than fifty species have now been identified, of which one half are recognized as pathogenic. Recent statistics indicate an increase in the prevalence and isolation of cervical lymphadenitis caused by NTM, far outnumbering TB as the cause of chronic cervical adenitis in children. The distinction has both diagnostic as well as therapeutic implications. Historically, scrofula was a term used to describe TB adenitis; however, NTM adenitis is included in the following text for completeness.
Pathophysiology
M tuberculosis is an obligate aerobe, nonspore forming, slender rod. Humans are its only reservoir. Transmission is from person to person via respiratory route by inhalation of small aerosols. After a short period of replication in the lungs, silent dissemination occurs through the lymphohematogenous system to extrapulmonary sites including the cervical lymph nodes.
NTM differs from M tuberculosis in several respects: (1) person-to-person transmission generally does not occur, and (2) NTM species are ubiquitous in nature and not necessarily pathogenic or equated with disease. The oral cavity may serve as a common portal of entry because the disease primarily occurs in children who have a propensity to put contaminated objects in their mouth.
Frequency
United States
Lymphadenitis is the primary manifestation of TB in 5% of the immunocompetent population, with the cervical lymph nodes providing the site of infection in two thirds of cases. In people with human immunodeficiency virus (HIV), cervical lymphadenitis may represent one third of the total presentations. Since 1985, the first increase in incidence since 1882 has occurred in the United States because of (1) increased immigration from endemic countries, (2) rising population of those infected with HIV, (3) worsening urban social conditions, and (4) abandonment of rigid TB control programs.
Currently 2-10% of mycobacterial infections in the United States are due to other NTM.
International
In impoverished countries where TB is endemic, TB continues to be a major health concern.
Mortality/Morbidity
- TB: The mortality rate approaches 20% with multidrug-resistant pulmonary TB. Statistics are not available for isolated cervical lymphadenitis.
- NTM: Recent statistics indicate an increase in prevalence and isolation of cervical lymphadenopathy caused by NTM. Because NTM is not generally reportable, the true incidence is difficult to determine.
Race
- TB: Incidence is increased in indigent, Asian, Hispanic immigrant, Native American, and Eskimo populations.
- NTM: People of all races are affected, with a white predominance.
Sex
- TB: The female-to-male ratio is 2:1.
- NTM: The female-to-male ratio is 1.3:1.
Age
- TB affects people of all ages.
- NTM affects children aged 1-5 years.
History
- M tuberculosis
- Patients report a painless, enlarging, or persistent mass.
- Systemic symptoms include fever/chills, weight loss, or malaise in 43% of patients.
- Nontuberculous mycobacterium
- Chronic cervicofacial mass
- Clinical progression of the disease
- No constitutional symptoms
- Poor response to conventional antibiotics
- No history of TB exposure
Physical
- M tuberculosis
- Any cervical node, although anterior cervical chain is more common
- Firm rubbery node becoming more firm and matted as disease progresses
- Infrequently, fluctuant with draining fistula
- Multiple masses in two thirds of patients
- Bilateral nodes in one third of patients
- Nontuberculous mycobacterium
- A nontender slightly fluctuant mass is present with the overlying skin obtaining a violaceous hue. This is referred to as a cold abscess because of its lack of calor, or warmth.
- As the lesion progresses, the skin can become adherent to the underlying mass. This stage may progress to rupture and sinus formation.
Causes
- Cellular immunity, in particular the T-cell population, is instrumental in controlling infection. Activated T cells generate cytokines that enable tissue macrophages and monocytes to destroy the mycobacteria and form a tubercle or granuloma. Therefore, in the population with HIV, the incidence of tuberculous infection is 500 times greater than in the general population.
- NTM generally occurs in immunocompetent hosts.
Cervicofacial Lymphangiomas
Congenital Malformations, Neck
Fine-Needle Aspiration of Neck Masses
Lymphomas of the Head and Neck
Malignant Nasopharyngeal Tumors
Neck Cancer, Unknown Primary Site
Neck, Cervical Metastases, Detection
Neck, Cysts
Ranulas and Plunging Ranulas
Salivary Gland Neoplasms
Thyroid Cancer
Other Problems to be Considered
Congenital-developmental problems (eg, sebaceous cyst, branchial cleft cyst, thyroglossal duct cyst, lymphangioma/hemangioma, dermoid, laryngocele, pharyngeal diverticulum, thymic cyst)
Infectious complications (eg, bacterial, viral, cat-scratch, actinomycosis, fungal, atypical mycobacterium)
Neoplastic complications (eg, metastatic, ie, unknown primary, epidermoid carcinoma, melanoma, adenocarcinoma; primary, ie, thyroid, lymphoma, salivary, lipoma, paraganglioma, rhabdomyosarcoma)
Lab Studies
- No specific laboratory tests are recommended for scrofula; however, the workup for a neck mass may include cat-scratch titers, CBC, and HIV test.
Imaging Studies
- CT scanning or MRI: Although both modalities can accurately depict sites, pattern, and extent of disease, they have limitations and findings are nonspecific. TB-infected nodes are frequently mistaken for metastatic carcinoma.
- Chest radiography
- TB: Despite the fact that cervical adenitis is usually secondary to a bronchopulmonary infection, review of the literature shows the rate of positive findings to be disappointingly low, averaging from 10-24% in patients with scrofula.
- NTM: Findings are normal.
Other Tests
- Purified protein derivative
- TB: Skin testing with partial purified protein derivative (PPD) has been fairly reliable. Generally, more than 85% of patients have a positive test of greater than 10 mm of induration. PPD should be the first line of investigation in the workup of a patient with a neck mass. Usefulness is diminished in individuals who have immunosuppression secondary to anergy.
- NTM: Response is variable. Known cross-reactivity to standard PPD exists, and induration typically is less than 10 mm. Skin test antigens for various NTM are available from the Centers for Disease Control and Prevention (CDC) in Atlanta. However, they are not commonly used secondary to lack of standardization, difficulty in interpretation, and ubiquity of organisms.
Procedures
- Fine-needle aspiration: Fine-needle aspiration is a useful initial procedure with a sensitivity of 77% and specificity of 93%. The positive predictive value approaches 100%. The most reliable criteria for diagnosing infection are the presence of stainable acid-fast bacilli and cultured organisms on aspirate. Granuloma formation is highly suggestive but not definitive. Cultures take 4-6 weeks for growth; however, the newer polymerase chain reaction (PCR) techniques are promising.
- Excisional or incisional biopsies
- TB: Biopsies are potentially hazardous because they may spread the disease and give rise to sinus formation.
- NTM: Excisional biopsy has both diagnostic as well as therapeutic efficacy.
Histologic Findings
M tuberculosis is referred to as an acid-fast bacillus secondary to its resistance to destaining by acid-alcohol treatment. The Ziehl-Neelsen technique demonstrates an obligate aerobe, a nonmotile, slender, slightly beaded, and bent rod. The presence of caseating granulomas may be observed.
Definitive diagnosis of NTM is based on objective identification of the organism by culture. NTM is characterized by specific growth characteristics and the ability to form pigments on culture.
Features claimed to be more representative of NTM lymphadenitis are (1) ill-defined or nonpalisading granulomas, (2) an irregular or serpiginous character of the granuloma, (3) a nonspecific granulomatous response with ill-defined aggregates of epithelial lymphocytes, (4) minimal or no caseous necrosis, (5) few giant cells, (6) variable sized granulomas in different stages of evolution, and (7) basophilic nuclear debris in the center of necrotic granulomas. However, the subjectivity of histopathologic interpretation of the above findings does not allow for conclusive diagnosis. Positive cultures are reported in most studies to be extremely difficult to obtain and are not necessary for diagnosis if other indicators are present, including age and presentation consistent with NTM, normal findings on chest radiograph, and weakly positive or negative PPD.
Medical Care
- M tuberculosis: In general, M tuberculosis infection is not considered a localized disease; therefore, systemic chemotherapy should be instituted. Medical treatment alone is the standard treatment for scrofula.
- Nontuberculous mycobacterium: Antituberculous therapy alone has substantial drawbacks in the treatment of NTM secondary to the lack of in vitro susceptibility. Recently, reports of the clinical efficacy of clarithromycin in patients with AIDS and Mycobacterium avium-intracellulare (MAI) complex have prompted its use in NTM lymphadenitis. The use is primarily based on anecdotal evidence, and clinical efficacy in the literature is sparse. The low incidence of NTM lymphadenitis has precluded controlled trials.
In a 2000 report, Starke recommends chemotherapy when the family refuses surgery, a recurrence after surgery occurs, or the surgeon can excise only a significant amount of abnormal tissue. The optimal treatment regimen is unknown (see Berger, 1996 for a proposed drug regimen). In 2005, Luong and McClay showed that over 50% of nontuberculous mycobacteria can respond to medical therapy, often times with clarithromycin (Biaxin) alone. If a 2-month trial of treatment shows no benefit, then surgical intervention should be considered.
Surgical Care
- M tuberculosis
- Surgery alone has had disappointing results and is plagued by a high rate of recurrence and fistulizations. Surgery is reserved for establishing the diagnosis, advanced local disease, persistent disease, or draining fistula.
- Failure to provide adequate chemotherapy at time of surgery may lead to postoperative fistulas and hematogenous spread.
- Nontuberculous mycobacterium
- Traditionally, surgical intervention ranging from simple aspiration to complete excision is the treatment of choice. Uniformly, simple incision and drainage is not recommended because of the high rate of fistulization and recurrence. Complete surgical excision is preferred; however, this procedure is not without risks, including injury to the facial nerve and scar formation with unacceptable cosmesis. If complete excision is attempted, removing all regional lymph nodes is not necessary because satellite nodes do not appear to be associated with recurrent disease.
- In order to circumvent complete excision and risking injury to facial nerve or poor cosmesis, two alternatives are available. In 1988, Alessi et al reported a series of 9 patients who underwent aspiration alone, all of whom had complete resolution. In 1992, Kennedy et al also described a series of 9 children who underwent curettage; no complications occurred, all healed without scarring, and no recurrence was documented with a follow-up of 6-20 months. In conclusion, complete excision of the offending nodes is the treatment of choice. However, when large areas of skin must be resected or the facial nerve is at risk, curettage or repeated needle aspiration serve as 2 efficacious alternatives.
Consultations
- Primary care or infectious disease physician
- Health department contact for TB
Antibiotic regimens effective for pulmonary infection can be applied to tuberculous lymphadenitis. Several options exist, including daily, twice weekly, and thrice weekly administration. The most common regimen consists of a 4-drug empiric treatment of isoniazid, rifampin, pyrazinamide, and ethambutol. After sensitivities return, continue 2 drugs for a total of 6 months.
Drug Category: Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
| Drug Name | Isoniazid (Laniazid, Nydrazid) |
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| Description | May inhibit mycolic acid synthesis resulting in disruption of bacterial cell wall. |
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| Adult Dose | 5 mg/kg PO/IM qd |
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| Pediatric Dose | 10-20 mg/kg PO/IM qd |
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| Contraindications | Documented hypersensitivity; previous isoniazid-associated hepatic injury or other severe adverse reactions |
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| Interactions | Higher incidence of isoniazid-related hepatitis can occur with alcohol ingestion on daily basis; aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum salts); may increase anticoagulant effects with coadministration; may inhibit metabolic clearance of benzodiazepines
Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function); coadministration with cycloserine may increase CNS side effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram
Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur |
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| Drug Name | Rifampin (Rifadin, Rimactane) |
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| Description | For use in combination with at least one other antituberculous drug; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur. |
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| Adult Dose | 600 mg PO qd |
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| Pediatric Dose | <5 years: Not established
> 5 years: 10-20 mg/kg PO qd |
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| Contraindications | Documented hypersensitivity; hepatic disease, alcoholism, coadministration with other hepatotoxic drugs (use caution and reduce dosages) |
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| Interactions | Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFT results occur) |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur |
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| Drug Name | Pyrazinamide |
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| Description | Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal depending on concentration of drug attained at site of infection; mechanism of action is unknown.
Administer for initial 2 mo of a 6-mo or longer treatment regimen for patients with drug-susceptible disease. Treat patients with drug-resistant disease with individualized regimens. |
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| Adult Dose | 20-30 mg/kg PO qd in divided doses |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe hepatic damage; acute gout |
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| Interactions | None reported |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Use only in combination with other effective antituberculous agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue drug if signs of hyperuricemia with acute gouty arthritis develop; perform baseline LFTs (closely monitor in liver disease); discontinue pyrazinamide if signs of hepatocellular damage appear; caution in history of diabetes mellitus |
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| Drug Name | Ethambutol hydrochloride (Myambutol) |
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| Description | Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which in turn causes cell death. No cross-resistance demonstrated.
Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been previously administered.
Administer q24h until permanent bacteriological conversion and maximal clinical improvement is observed. Absorption is not significantly altered by food. |
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| Adult Dose | 15 mg/kg PO qd |
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| Pediatric Dose | <12 years: Not established
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; optic neuritis (unless clinically indicated) |
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| Interactions | Aluminum salts may delay and reduce absorption (administer several h before or after ethambutol dose) |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Assess visual status before therapy; test visual acuity and color discrimination monthly; monitor renal and liver functions |
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Further Outpatient Care
- Baseline tests prior to medical treatment include hepatic function, bilirubin, BUN/creatinine, and platelet count.
- Clinically monitor patients once a month. Initiate laboratory monitoring if symptoms suggest toxicity. Some recommend liver function tests at least in the first and third months. Obtain uric acid levels for pyrazinamide toxicity and assess visual acuity for ethambutol toxicity.
In/Out Patient Meds
Complications
- M tuberculosis
- Disseminated disease
- Chronic draining fistula
- Nontuberculous mycobacterium - Scar formation
Prognosis
- M tuberculosis: Clinical remission rates approach 100% with medical treatment.
- Nontuberculous mycobacterium: Clinical remission rates are greater than 95% with surgical treatment.
Patient Education
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Scrofula excerpt Article Last Updated: Jun 9, 2006
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