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Scrofula

Scrofulas

Scrofula which is also known as infectious cervical lymphadenitis is a general term used to define the tuberculous or nontuberculous mycobacterial infections of the lymph nodes in the cervix. This clinical condition is commonly seen in tuberculosis (TB) endemic region and among immunosuppressed patient in the developed countries. Tuberculous cervical lymphadenitis is also referred as scrofula or king's evil.


Presentation

Common systemic manifestations of scrofula include fever, chills, reduced weight, and malaise. Reported cases of painless, continuous growth of mass have being observed in some patients. A densely hard, tangled mass with an overlying skin resulting in its purple discoloration is seen. This is known as the cold abscess because of the color or warm nature of the mass. With the progressive development of this lesion, the skin may align or adhere with the underlying mass. This could progressively lead to the rupture of the mass or sinus formation. Scrofula is mainly associated with the lymph nodes located at the posterior side of the cervix and supraclavicular chains. An infection by the mycobacterium in the related tissue is believed to result from intrathoracic lymphatics by the contiguous spread. Also, an enlargement of the mediastinal lymph nodes is usually observed in conditions involving primary pulmonary diseases. Scrofula may result in the formation of typically noninflamed lymph nodes which are discrete and hard when compared with the features seen in lymphadenopathy conditions (characterized by acutely inflamed lymph nodes). A densely hard, tangled mass of lymph nodes may become visible with disease progression and may form a fluctuant swelling with draining fistula in an untreated lymphadenopathy. The enlarged nodes may apply pressure on the esophagus, leading to dysphagia. Systemic symptoms vary and are more common among the immunocompromised patients. However, in few immunocompromised patients in which there is an absence of systemic manifestations, concomitant pulmonary tuberculosis may be seen in more than 50% of the affected cases [6]. Scrofula or cervical tuberculous lymphadenitis may be characterized by gradual enlargement of the affected lymph nodes. In severe cases, the nodes may be inflamed and painful; resulting in the ulceration of the overlying skin with draining fistula. The most commonly manifested form of extrapulmonary tuberculosis is the cervical lymphadenitis. Peripheral tuberculous lymphadenitis may also be seen as the presenting form of extrapulmonary TB. Patients with cervical tuberculous lymphadenitis usually present with gradually enlarging, painless cervical lymph nodes, which may persist for about 1 year before detection [7].

The most usually affected lymph nodes in tuberculous lymphadenitis are cervical nodes with the prevalence of approximately 63% in reported cases. Others include mediastinal nodes (27%) including axillary nodes (8%). In the neck, different types of lymph nodes are more usually affected compared to others, with a specific predilection for lymph nodes at the posterior triangle (51%) and deep anterior cervical triangle (48%). Major cases of lymphadenitis are unilateral.

Constitutional Symptom
  • The most common observation was unilateral, matted adenopathy in female patients aged between 11 and 20 years and without constitutional symptoms of tuberculosis.[ncbi.nlm.nih.gov]
  • NTM infections do not show other notable constitutional symptoms, but scrofula caused by tuberculosis is usually accompanied by other symptoms of the disease, such as fever, chills, malaise and weight loss in about 43% of the patients.[findmeacure.com]
  • symptoms Poor response to conventional antibiotics No history of tuberculosis exposure A nontender slightly fluctuant mass is present with the overlying skin obtaining a violaceous hue.[emedicine.com]
Vietnamese
  • ) Ido (io) Indonesian (id) Interlingue (ie) Italian (it) Japanese (ja) Kurdish Kurmanji (ku) Latin (la) Maori (mi) Mongolian (mn) Persian (fa) Polish (pl) Portuguese (pt) Russian (ru) Slovak (sk) Slovenian (sl) Spanish (es) Swahili (sw) Turkish (tr) Vietnamese[glosbe.com]
  • English - German Skrofulose 180 millions of speakers Translator English - Japanese 腺病 130 millions of speakers Translator English - Korean 연주창 85 millions of speakers Translator English - Javanese Scrofula 85 millions of speakers Translator English - Vietnamese[educalingo.com]
Turkish
  • Hungarian (hu) Ido (io) Indonesian (id) Interlingue (ie) Italian (it) Japanese (ja) Kurdish Kurmanji (ku) Latin (la) Maori (mi) Mongolian (mn) Persian (fa) Polish (pl) Portuguese (pt) Russian (ru) Slovak (sk) Slovenian (sl) Spanish (es) Swahili (sw) Turkish[glosbe.com]
  • Scrofula 85 millions of speakers Translator English - Vietnamese bịnh tràng nhạc 80 millions of speakers Translator English - Tamil கண்டமாலை 75 millions of speakers Translator English - Marathi गंडमाळे 75 millions of speakers Translator English - Turkish[educalingo.com]
Cervical Lymphadenopathy
  • METHODS AND RESULTS: A total of 1827 patients with cervical lymphadenopathy who presented to various out-patients clinics of our institution were studied over a three-year period.[ncbi.nlm.nih.gov]
  • Methods and results: A total of 1827 patients with cervical lymphadenopathy who presented to various out-patients clinics of our institution were studied over a three-year period.[cambridge.org]
  • lymphadenopathy and tuberculosis of adjacent skin (lupus vulgaris), with chronic draining sinuses below the angle of the jaw and cervical region.[medical-dictionary.thefreedictionary.com]
  • It allows proper examination of the cervical lymphadenopathy and assists in guiding during the procedure of fine needle aspiration cytology (FNAC).[symptoma.com]
  • Recent statistics for NTM 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.[emedicine.com]
Vascular Disease
  • Scrofula has been mistaken for metastatic carcinoma, regional neoplasms, thyroglossal duct cysts, fungal disease, toxoplasmosis, lymphoma, osteosarcoma, chondrosarcoma, bacterial adenitis, and collagen vascular disease.[ncbi.nlm.nih.gov]
Eye Swelling
  • In addition to the main manifestations of the disease, there may be secondary symptoms, such as inflammation of the eyes, swelling of the joints, bloating, dischargeexcretions from the ears and nose, even convulsions.[euromd.com]
Fair Complexion
Neck Mass
  • Therefore, to ensure the patient of the most beneficial therapy, the physician must always consider scrofula in the differential diagnosis of a neck mass, and particularly because of the increases incidence of intrapulmonary tuberculosis in AIDS patients[ncbi.nlm.nih.gov]
  • A 39-year-old Zambian man who was visiting the United States presented with a three-week history of a draining neck mass and a three-month history of swelling on the left side of his neck.[nejm.org]
  • Combinations based on Infectious Disease input. 2-year-old girl with 4 weeks of painless right neck mass that has not responded to antibiotics. View Case[ajnr.org]
  • 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. For nontuberculous mycobacterium (NTM), response is variable.[emedicine.com]
Neck Mass
  • Therefore, to ensure the patient of the most beneficial therapy, the physician must always consider scrofula in the differential diagnosis of a neck mass, and particularly because of the increases incidence of intrapulmonary tuberculosis in AIDS patients[ncbi.nlm.nih.gov]
  • A 39-year-old Zambian man who was visiting the United States presented with a three-week history of a draining neck mass and a three-month history of swelling on the left side of his neck.[nejm.org]
  • Combinations based on Infectious Disease input. 2-year-old girl with 4 weeks of painless right neck mass that has not responded to antibiotics. View Case[ajnr.org]
  • 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. For nontuberculous mycobacterium (NTM), response is variable.[emedicine.com]
Cranial Neuropathy
  • A middle-aged woman presenting with multiple cranial neuropathies, hemiparesis, and CSF pleocytosis had tuberculous infection of the cranial dura mater at autopsy. This is the first description of dural scrofula in modern medical literature.[ncbi.nlm.nih.gov]

Workup

The diagnosis of scrofula is similar to the pulmonary TB, which includes chest x-ray, tuberculin skin test, interferon-gamma-release assay, microscopy (involving the use of special staining technique) and mycobacterial cultures. Different samples such as cerebrospinal fluid (CSF), pleural fluid, pericardial or another aspirate can be used for mycobacterial culture. Also, nucleic acid testing such as polymerase chain reaction (PCR), nucleic hybridization technique may be done on the freshly taken body fluids, biopsy or fixed tissue samples. Most often, hematological analysis of the body fluids usually shows a remarked increase in lymphocytes. Estimation of CSF glucose with the result showing an increase of more than 50% compared with serum glucose, along with an elevated protein level is highly suggestive of scrofula. Furthermore, common clinical symptoms associated with tuberculosis infection may be observed. These include fever, night sweats, reduced weight, and purulent cough. In conclusion, the inflamed lymph node may be examined for related features of scrofula which include an enlarged, painless growth, which may be erythematous, possibly enclosed with drainage.

Lymph nodes which appear with central lucency in computed tomography (CT scan) are usually abnormal, indicating either necrosis or tumor infiltration of the node. A peripheral contrast adjustment may show excessive blood draining in the inflamed lymph node mass or increased vascularization of the lymph node. Scrofula appears in different forms following imaging examination depending upon the progression state of the condition. In early infectious stage, nonnecrotic nodes show a homogeneous signal intensity with increased homogeneity in contrast by both CT scan and magnetic resonance (MRI) imaging. As the disease condition progresses with necrosis of the nodes, CT images show features of central low density that indicate the necrotic parts and thick circle of progression. The main mode of diagnosis is tissue biopsy, which allows proper histological examination, mycobacterium species differentiation, and antibiotic sensitivity testing. Another diagnostic technique such as fine-needle aspiration has a sensitivity of 52.9% when used alone, with an increased sensitivity of 82% in combination with PCR [8]. Also, identification of epithelioid histiocytes, dead cells, mycobacterium bacteria, and langhans multinucleated giant (MGCs) cells indicates tuberculous scrofula. After laboratory culture of AFB in the media, specific mycobacterium DNA probe may be used in testing the mycobacterium. Different specific probes are available for each mycobacterium species, these include, M. kansasii, M. avium, and M. gordonae. Also, a tuberculin skin (Mantoux) test can be used to diagnose tuberculosis infection with some degree of sensitivity using partially purified protein derivative (PPD). Most often, more than 85% cases of tested patients are positive, having an induration diameter on the skin spot greater than 10 mm.

In designing a work up plan for a suspected patient with neck tumor, Mantoux test should be the initial line of diagnosis to rule out tuberculosis infection. However, the chances of establishing the right diagnosis may be hindered in an immunosuppressed patient. In this type of patient, fine-needle aspiration cytology (FNAC) is an effective diagnostic procedure with reported high sensitivity (77%) and specificity (93%) of detection with positive predictive value of about 100%. The best method for diagnosing tuberculosis infection is to demonstrate the presence of the bacteria which are acid-fast bacilli using a staining technique and culturing the aspirate sample in a culture media.

Fine-needle aspiration of cytological fluid could be used to establish the diagnosis, however, excisional biopsy has proven to be more sensitive. Diagnostic results from nucleic acid amplification methods are not dependable [9] [10]. The use of imaging can not be singly used to effectively differentiate between lymphadenitis of tuberculous etiology and other types of cervical lymphadenopathy, necrotic or cystic lymphadenopathy. Therefore, patient history or demographic information is important for proper interpretation of the imaging results. The previous study revealed that abnormal features of chest radiograph are observed in almost half of the scrofula patient population [5].
Ultrasound is one of the effective method used in making an early diagnosis of scrofula. It allows proper examination of the cervical lymphadenopathy and assists in guiding during the procedure of fine needle aspiration cytology (FNAC). An adapted method which combines grey-scale imaging with FNAC displayed high sensitivity (92%) and specificity (97%) in differentiating between benign and malignant nodal disease [9]. Common features of tuberculous lymphadenitis on gray scale imaging that helps to differentiate from cervical carcinoma include, nodal matting and edema of related soft tissue causing abnormal enlargement in the cervix. Doppler examination is another technique that is useful to distinguish tuberculous infection from other necrotic metastatic disease [9]. Increased vascularity usually at the hilum is commonly seen in reactive lymph nodes including those associated with tuberculous lymphadenitis, while malignant nodes have features of peripheral or capsular vascularity.

The appearance of tuberculous lymphadenitis in CT examination varies, depending on the degree or level of caseation of the lymph node. Most often, the nodes may have an enlarged appearance usually with attenuation closely similar to the muscle cells. This may progressively develop into central caseation of the node, formation of a cyst after the nodes have become centrally less dense. MRI features are related to the CT result, ranging from homogeneously enlarged lymph nodes to the cystic formation with peripheral involvement.

Treatment

Medication is the major means of treating tuberculosis infections following strict, monitored regimen and guidelines. Presently, the standard drug regimen of choice for the scrofula treatment caused by M. tuberculosis are used in phases. Most commonly, the treatment comprises of a 4-drug empiric therapy. These include isoniazid (INH), rifampin (RFA), pyrazinamide (PZA), and ethambutol (EMB). The initial phase of treatment involves administration of the 4-drug regimen for the first 8 weeks, followed by a continuation phase of isoniazid and rifampin for 6-12 months. During the management of tuberculosis infection, complications observed by lymphadenopathy are usually due to the immunological response to the dead microorganism. Surgical intervention is usually recommended for severe conditions which include abscess development and draining sinuses.

Infections with NTM may be managed conservatively along with surgical corrections when necessary. Recommended treatment is the total surgical excision of the affected tissue. However, aspiration or curettage method with antibiotic regimen may be employed if the lesions are located closer to the facial nerve or related branches. Systemic chemotherapy should be used in treating mycobacterium tuberculosis infection because it is generally not classified as a localized disease. The antibiotic drugs which are effective in treating the pulmonary infection can also be used to manage tuberculous lymphadenitis. This may be given in phases with different dosage starting with a daily dose, weekly (twice or thrice), and monthly administration. Continuous drug regimen for about 6-9 months is adequate enough for treating systemic infections except for meningeal involvement, where the treatment may be extended for about 9-12 months. Surgical methods may not be necessary for managing TB lymphadenitis except in establishing the diagnosis. Special support and attention must be given to the patient care. These include respiratory isolation of admitted patient in the hospital, comprehensive laboratory investigations, imaging examination (e.g chest X-ray). Laboratory test such as sputum acid-fast bacilli (AFB) microscopy, FNAC of the lesion is helpful in making the right diagnosis including purified protein derivative skin test, which may be needed to make an urgent diagnosis. The standard guideline recommended by the Infectious Diseases Society of America (IDSA) is a 6-month regimen of antibiotics. Although, the use of corticosteroids in treatment is not a common practice [5], however, prednisone may be administered to reduce patient’s venous obstruction and prevent a subsequent paradoxical reaction. This reaction could be in the form of deterioration of the existing lesions, or the development of new lesions, after an initial resolution [11] and may result from an extensive immunological response to the mycobacterial antigens after the onset of treatment [5].

Prognosis

The prognosis following treatment of scrofula with mycobacterium tuberculosis etiology is 100% while that of the nontuberculous mycobacterium has shown clinical remission rates higher than 95% following surgical intervention.

Etiology

Generally, 95% of the adult cases of scrofula result from infection with mycobacterium tuberculosis, while others are due to infection by non-tuberculosis mycobacterium (NTM). These NTM include mycobacterium avium, mycobacterium intracellulare, mycobacterium scrofulaceum, mycobacterium kansasii, and M. chelonae. However, the incidence of scrofula in children is in contrast with the adult cases with NTM infection resulting into 92% of known cases [1]. Most of the adult cases are treated by pharmacological therapy while those in children often require surgical intervention. Among the different forms of extrapulmonary TB, scrofula is the most prevalent; presenting as the main form of the condition in about 5% of the observed cases. Among immunosuppressed patients, scrofula may be seen as the major form of TB in one-third of cases [2].

Epidemiology

As previously stated, TB lymphadenitis is the most commonly known form of extrapulmonary TB [3] and major cause of a peripheral lymphadenitis in the developing countries. In scrofula resulting from TB infection, the ratio of prevalence between male and female is 1:2, affecting individuals without any age difference while those of NTM origin, the gender difference ratio of male to female is 1:1.3. However, NTM mostly affects children between the age of 1-5 years. Lymphadenitis is usually the primary presentation seen in tuberculosis infection among 5% of the immunosuppressed population, where the cervical lymph nodes serve as the route of infection in two-third of reported cases. Among human immunodeficiency virus (HIV) infected patients, cervical lymphadenitis may be seen as the major presentation in affected individuals. The epidemiology and diagnosis of scrofula vary depending on the patients’ geographical background and the load of the TB or HIV infection [4].
Most often, the affected populations are the children and young adults (usually between 11-30 years) with slightly higher incidence among female population [5].

Sex distribution
Age distribution

Pathophysiology

Mycobacterium tuberculosis bacteria are obligate aerobic microorganisms. They are non–spore forming and have slender rod appearance. The only reservoir host is human and the mode of transmission is through contact with the infected person via respiratory inhalation of small droplets or aerosols. Following few periods of replication of the bacteria in the lungs, it silently disseminates into the extrapulmonary sites such as the cervical lymph nodes via the lymphohematogenous system. Immunity confers by the immune cells mainly by T-cell production. Activated T cells help to stimulate cytokine production that enhances tissue macrophages and monocytes to phagocytose the mycobacteria resulting in the formation of a tubercle or granuloma.

Prevention

There are two approaches to preventing scrofula. One is directed at eliminating the spread of tuberculosis infection. Also, the early infection can be prevented from progressing into an active disease. Generally, TB can be prevented by room ventilation, mouth covering and wearing of nose mask where necessary. TB vaccines are also available for high-risk individuals.

Summary

Scrofula is derived from a Latin word meaning 'brood sow', which is used to describe tuberculosis affecting the neck. However, an infection of the cervix associated lymph nodes (lymphadenitis) usually results into cervical tuberculosis. Extrapulmonary tuberculosis, including scrofula, are commonly seen in the immunocompromised patient, and it is responsible for 50% cases of the cervical infections.

Patient Information

Scrofula is a term which describes the infection of the lymph node of the cervix by mycobacterium or non-mycobacterium tuberculosis bacteria. It is also referred to as infectious cervical lymphadenitis or king's evil. It is commonly seen in the immunosuppressed patient and endemic region of tuberculosis infection. Lymphadenitis of tuberculosis origin is the usually known type of extrapulmonary TB and the main cause of other types of lymphadenitis in the developing countries. Scrofula caused by TB infection usually affect the female than male although with no age difference while those of NTM mostly affect the children between the age of 1-5 years. The signs of scrofula may be related to the ones seen in pulmonary tuberculosis. Common manifestations in scrofula include, fever, chills, reduced weight, and malaise and cases of painless, continuous growth of mass have been observed in some patients. This mass may cause purple discoloration of the skin of the affected part and rupture. The patient may also show sign of lymph node enlargement of the neck. Suspected patient with scrofula features and high-risk individual, including those with neck mass can be examined by physicians. The patients are managed with supportive care by admitting them in a special ward and screened using the different diagnostic techniques. Different investigations such as chest X-ray, sputum AFB, or a purified protein derivative skin test may be done. Also, CT scan and fine-needle aspiration biopsy of the affected part may be required. Differential diagnosis is very important because scrofula presentation may mimic other diseases. Although laboratory test of the biopsy or culture samples aid in establishing the diagnosis, physicians can make an early diagnosis from the features observed from the scan result. Diagnosed patients are treated with drugs recommended by the physicians and may take up to 12 months for the disease to be cured. Sometimes, surgical intervention may be used in patient management depending on the judgment of the physician.

References

Article

  1. Albright JT, Pransky SM. Nontuberculous mycobacterial infections of the head and neck. Pediatr Clin North Am. 2003; 50(2): 503-14.
  2. Clay J. Scrofula.www.emedicine.com/ent/topic524.htm, Accessed 20 Sept 2008.
  3. Ilgazli A, Boyaci H, Basyigit I, Yildiz F. Extrapulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. Arch Med Res. 2004; 35(5): 435-41.
  4. Weis SE, Moonan PK, Pogoda JM, et al. Tuberculosis in the foreign-born population of Tarrant county, Texas by immigration status. Am J Respir Crit Care Med. 2001; 164(6): 953-7.
  5. Jha BC, Dass A, Nagarkar NM, et al. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgrad Med J. 2001;77 (905): 185-7. doi:10.1136/pmj.77.905.185
  6. Fontanilla JM, Barnes A, von Reyn CF. Current diagnosis and management of peripheral tuberculous lymphadenitis. Clin Infect Dis. 2011; 53(6): 555-62.
  7. Mert A, Tabak F, Ozaras R, Tahan V, Oztürk R, Aktuğlu Y. Tuberculous lymphadenopathy in adults: a review of 35 cases. Acta Chir Belg. 2002; 102(2): 118-21.
  8. Goel MM, Ranjan V, Dhole TN, et al. Polymerase chain reaction vs. conventional diagnosis in fine needle aspirates of tuberculous lymph nodes. Acta Cytol. 2001; 45(3):333-40.
  9. Daley P, Thomas S, Pai M. Nucleic acid amplification tests for the diagnosis of tuberculous lymphadenitis: a systematic review. Int J Tuberc Lung Dis. 2007;11(11):1166-76.
  10. Ahuja A, Ying M, Yuen YH, et al. Power Doppler sonography to differentiate tuberculous cervical lymphadenopathy from nasopharyngeal carcinoma. AJNR Am J Neuroradiol. 2001;22 (4): 735-40.
  11. Park KH, Cho OH, Chong YP, et al. Post-therapy paradoxical response in immunocompetent patients with lymph node tuberculosis. J Infect. 2010; 61(5): 430-4.

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Last updated: 2019-07-11 22:43