Monte S Meltzer, MD,
Chief, Dermatology Service, Union Memorial
Hospital
Nothing to disclose.
Coauthor(s)
Carol A Nacy, PhD,
Adjunct Professor, Department of Biology,
Catholic University of America; Adjunct Professor, Department
of Tropical Medicine and Microbiology, George Washington
University
Sequella, Inc. Ownership
interest Employment; Sequella,
Inc. Ownership
interest investor
Specialty Editor(s)
Catherine M Quirk, MD,
Clinical Assistant Professor, Department of
Dermatology, University of Pennsylvania
Nothing to disclose.
Jeffrey Meffert, MD,
Assistant Clinical Professor of Dermatology,
University of Texas Health Science Center-San
Antonio
Nothing to disclose.
Richard P Vinson, MD,
Assistant Clinical Professor, Department of
Dermatology, Texas Tech University School of Medicine;
Consulting Staff, Mountain View Dermatology,
PA
Nothing to disclose.
Shyam Verma, MBBS, DVD, FAAD,
Adjunct Clinical Assistant Professor,
Department of Dermatology, University of Virginia, State
University of New York at Stonybrook, Penn State
University
Nothing to disclose.
Chief Editor
Dirk M Elston, MD,
Director, Department of Dermatology,
Geisinger Medical Center
Nothing to disclose.
Background
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB) and a member of a group of closely related organisms in the M tuberculosis complex: Mycobacterium africanum, Mycobacterium bovis, Mycobacterium microti, and M tuberculosis. In 1882, Robert Koch discovered and isolated the tubercle bacillus (M tuberculosis).
TB is an ancient disease. Signs of skeletal TB (Pott disease) were evident in Europe from Neolithic times (8000 BCE), in ancient Egypt (1000 BCE), and in the pre-Columbian New World. TB was recognized as a contagious disease by the time of Hippocrates (400 BCE), when it was termed "phthisis" (Greek from phthinein, to waste away).
World incidence of TB increased with population density and urban development so that by the Industrial Revolution in Europe (1750), it was responsible for more than 25% of adult deaths. Indeed, in the early 20th century, TB was the leading cause of death in the United States. Neil Finsen won the Nobel Prize in Medicine in 1903 for introducing UV light into the treatment of skin TB.
With the improvement of living conditions and the introduction of effective treatment (streptomycin) in the late 1940s, the number of reported TB patients in the United States steadily declined (126,000 TB patients in 1944, 84,000 in 1953, 22,000 in 1984, and 14,000 in 2004) despite explosive growth in the total population (140 million people in 1946, 185 million in 1960, and 226 million in 1980).
Microbiology
Mycobacteria are aerobic, nonsporeforming, nonmotile, facultative, intracellular, curved rods measuring 0.2-0.5 by 2-4 μ m. Their cell walls contain mycolic acid-rich long-chain glycolipids and phospholipoglycans (mycocides) that protect mycobacteria from cell lysosomal attack and also retain red basic fuchsin dye after acid rinsing (acid-fast stain).
The Ziehl-Neelson acid-fast stain, while highly specific for mycobacteria, is relatively insensitive, and detection requires at least 10,000 bacilli per mL; most clinical laboratories currently use a more sensitive auramine-rhodamine fluorescent stain (auramine O).
Routine culture uses a nonselective egg medium (Lowenstein-Jensen or Middlebrook 7H10) and often requires more than 3-4 weeks to grow because of the 22-hour doubling time of M tuberculosis. Radiometric broth culture (BACTEC radiometric system) of clinical specimens significantly reduces time (10-14 d) for mycobacterial recovery.
DNA probes specific for mycobacterial ribosomal RNA identify species of clinically significant isolates after recovery. In tissue, polymerase chain reaction (PCR) amplification techniques can be used to detect M tuberculosis -specific DNA sequences and thus, small numbers of mycobacteria in clinical specimens.[1, 2]
TB is an airborne communicable disease that occurs after inhalation of infectious droplets expelled from patients with laryngeal or pulmonary TB during coughing, sneezing, or speaking. Each cough can generate more than 3000 infectious droplets. Droplets are so small (1-5 μ m) that they remain airborne for hours.
The probability that disease transmission will occur depends upon the infectiousness of the tuberculous patient, the environment in which exposure takes place, and the duration of exposure. Approximately 20% of people in household contact develop infection (tuberculin skin test positive). Microepidemics have occurred in closed environments such as transcontinental flights and submarines. Tuberculin sensitivity develops 2-10 weeks after infection and usually is lifelong.
Without treatment, an approximate 10% lifetime chance exists of developing active disease after TB infection (5% within the first 2 years, 5% thereafter). Increased risk of acquiring active disease occurs with HIV infection (100-fold risk overall, 10% chance per year), IV drug abuse, diabetes mellitus (3-fold risk), silicosis, immunosuppressive therapy, cancer of the head and neck, hematologic malignancies, end-stage renal disease, intestinal bypass surgery or gastrectomy, chronic malabsorption syndromes, low body weight, and in infants younger than 2 years.
Because TB induces a strong immune response, individuals with positive tuberculin reactions are at a significantly lower risk of acquiring new TB infection. In HIV-infected individuals, active TB more likely occurs from reactivation of existing disease than from superinfection with a new mycobacterial strain.
Pathogenesis
The typical TB lesion is epithelioid granuloma with central caseation necrosis. The most common site of the primary lesion is within alveolar macrophages in subpleural regions of the lung. Bacilli proliferate locally and spread through the lymphatics to a hilar node, forming the Ghon complex.
Early tubercles are spherical 0.5- to 3-mm nodules with 3 or 4 cellular zones demonstrating (1) a central caseation necrosis, (2) an inner cellular zone of epithelioid macrophages and Langhans giant cells admixed with lymphocytes, (3) an outer cellular zone of lymphocytes, plasma cells, and immature macrophages, and (4) a rim of fibrosis in healing lesions.
Initial lesions may heal and the infection becomes latent before symptomatic disease occurs. Smaller tubercles may resolve completely. Fibrosis occurs when hydrolytic enzymes dissolve tubercles, and larger lesions are surrounded by a fibrous capsule. Such fibrocaseous nodules usually contain viable mycobacteria and are potential lifelong foci for reactivation or cavitation. Some nodules calcify or ossify and are seen easily on chest x-ray. Tissues within areas of caseation necrosis have high levels of fatty acids, low pH, and low oxygen tension, all of which inhibit growth of the tubercle bacillus.
If the host is unable to arrest the initial infection, the patient develops progressive primary TB with tuberculous pneumonia in the lower and middle lobes of the lung. Purulent exudates with large numbers of acid-fast bacilli can be found in sputum and tissue. Subserosal granulomas may rupture into the pleural or pericardial spaces and create serous inflammation and effusions.
With the onset of host-immune response, lesions that develop around mycobacterial foci can be either proliferative or exudative. Both types of lesions develop in the same host, since infective dose and local immunity vary from site to site.
Proliferative lesions develop where the bacillary load is small and host cellular-immune responses dominate. These tubercles are compact with activated macrophages admixed and are surrounded by proliferating lymphocytes, plasma cells, and an outer rim of fibrosis. Intracellular killing of mycobacteria is effective, and the bacillary load remains low.
Exudative lesions predominate when large numbers of bacilli are present and host defenses are weak. These loose aggregates of immature macrophages, neutrophils, fibrin, and caseation necrosis are sites of mycobacterial growth. Without treatment, these lesions progress and infection spreads.
Although mycobacteria are spread by blood throughout the body during initial infection, primary extrapulmonary disease is rare except in severely immunocompromised hosts. Resistant hosts control mycobacterial growth at distant foci before development of active disease. Infants, older persons, or otherwise immunosuppressed hosts are unable to control mycobacterial growth and develop disseminated (primary miliary) TB. Patients who become immunocompromised months to years after primary infection also can develop late generalized disease.
The lungs are the most common site for TB disease: 85% of TB patients present with pulmonary complaints. Extrapulmonary TB can occur as part of a primary or late generalized infection or as a reactivation site that may coexist with pulmonary reactivation. The most common sites of extrapulmonary disease are mediastinal, retroperitoneal, and cervical (scrofula) lymph nodes, vertebral bodes, adrenals, meninges, and the GI tract. Pathology of these lesions is similar to those in the lung.
Cutaneous tuberculosis
Although 1 of 3 individuals on this planet is infected with tubercle bacillus, the incidence of cutaneous TB appears low. In areas such as India or China where TB prevalence is high, cutaneous manifestations of TB (overt infection or tuberculids) are found in less than 0.1% of individuals seen in dermatology clinics.
In a 10-year (1983-1992) retrospective survey of patients seen in governmental dermatology clinics in Hong Kong, the detected incidence of cutaneous TB among patients was 179 per 267,089 (0.07%). Among patients with cutaneous TB, 15% had classic cutaneous TB (approximately 5% each of lupus vulgaris, TB verrucosa cutis, and scrofuloderma), and 85% had tuberculids.
In a tertiary-care hospital in northern India, 0.1% of dermatology patients seen from 1975-1995 had cutaneous TB. Lupus vulgaris was the most frequent manifestation (55%), followed by scrofuloderma (27%), TB verrucosa cutis (6%), tuberculous gumma (5%), and tuberculids (7%).
The incidence of patients with cutaneous TB seen from 1980-1993 in a hospital dermatology clinic in Madrid was 16 (0.14%) in 10,304.
Alarmingly, the number of reported patients with TB in the United States has been increasing since 1985 such that TB has reemerged as a serious national problem. In 1998, researchers reported 18,361 patients with TB; the rate of TB infection was 6.8 cases per 100,000 population. California, Florida, Illinois, New York, and Texas reported 54% of TB occurrences.
The proportion of TB patients who were foreign-born individuals was 42%. Persons born in Mexico, the Philippines, and Vietnam account for one half of foreign-born TB patients in the United States. The TB rate among foreign-born persons was 4-6 times higher than for US-born persons. Minimum estimates of the proportion of TB patients with coincident HIV infection were approximately 10-15%. Among persons aged 25-44 years, this proportion increased to 20-30%.
The underlying basis of this new TB epidemic reflects a minimum of four major factors including (1) the association of TB with the HIV epidemic, (2) increased immigration from countries where TB is common, (3) transmission of TB in congested settings (health-care facilities, prisons, homeless shelters), and (4) the deterioration of basic health-care infrastructure.
Molecular typing of M tuberculosis isolates in the United States by restriction fragment-length polymorphism analysis suggests more than one third of new patient occurrences result from person-to-person transmission, and the remainder result from reactivation of latent infection. Approximately 1 of 13 M tuberculosis isolates currently shows a form of drug resistance.
The recent introduction of biological agents that block tumor necrosis factor-alpha in the treatment of rheumatoid arthritis, psoriasis, and several other autoimmune disorders has further raised concern for the identification of patients with latent TB. Currently, several hundred cases of TB disease have been reported in patients who receive these tumor necrosis factor-alpha antagonists.
International
The current global burden of TB boggles the mind. In 1997, the incidence of new TB patients approached 8 million in addition to more than 16 million existing patients. Approximately 2 million people died of TB in 1997 with a global fatality rate of 23% (fatality rates exceed 50% in some African countries with high HIV incidence). The estimate of the proportion of TB patients with coincident HIV infection is approximately 8%.
Among infectious diseases, TB is the leading cause of death. TB was responsible for 6% of deaths worldwide. Global prevalence of TB currently is greater than 32%. More than 50% of new patient occurrences were in 5 Asian countries, ie, India (largest worldwide patient load), China, Indonesia, Bangladesh, and Pakistan.
Sex
Male-to-female ratio is 1.35:1.
Age
Although no age group is exempt, most patients show clinical infection within the first 3 decades of life.
Primary-inoculation TB results from direct introduction of mycobacteria into the skin or mucosa of an individual who was not previously infected with TB or was immunized with the M bovis strain bacille Calmette-Guérin (BCG). Since mycobacteria do not penetrate intact skin, initiation of infection almost always follows an injury, usually in children. Common sites include the face and other exposed skin. Tuberculous chancres are reported after ritual circumcision, tattooing, ear piercing, venipuncture, sexual intercourse, tooth extraction, and after ingestion of milk contaminated with M bovis. Primary-inoculation TB also is reported after M bovis BCG immunotherapy for malignant melanoma.
After mycobacteria gain entry into the skin, they multiply in tissue macrophages and spread to regional lymph nodes. An inflammatory papule develops in 2-4 weeks at the inoculation site that breaks down into a firm, nonhealing, shallow, nontender, undermined ulcer with a granulomatous base. Painless regional lymphadenopathy is evident at 3-8 weeks. Numerous bacilli are present at the inoculation site and regional node. This ulceroglandular complex is the skin analog to the Ghon complex.
As with all TB infections, the clinical course depends upon the host-immune response. Tuberculin sensitivity usually is coincident with the development of lymphadenopathy. Epithelioid granulomas are evident in the skin and lymph nodes. Numbers of tubercle bacilli progressively decrease. The primary lesion heals with scarring after 1-3 months. With a less effective host-immune response, bacterial load remains high and healing is delayed for up to 12 months. Regional nodes may suppurate, erode, and perforate the surface of overlying skin (scrofuloderma). Latent foci of infection can remain at the site and progress to lupus vulgaris or TB verrucosa cutis despite evident tuberculin sensitivity. Hematogenous dissemination of mycobacteria from skin can result in TB at other sites (particularly bones and joints) or progress catastrophically to acute miliary disease with a fatal outcome.
TB verrucosa cutis
TB verrucosa cutis is an indolent warty plaque that occurs after direct inoculation of TB into the skin of individuals previously infected with M tuberculosis or M bovis. Reinfection TB can result from accidental exposure to tuberculous tissue in high-risk groups, such as physicians, pathologists, and laboratory workers (anatomists' wart, prosectors' wart, verruca necrogenica). Farmers, butchers, and veterinarians contract this form of reinfection TB from tuberculous cattle. Individuals, especially children from lower socioeconomic groups, also can contract this lesion after contact with tuberculous sputum. In countries such as India, walking barefoot and the habit of spitting associated with betel leaf (paan) chewing are worth noting.
Lesions most commonly occur on the hands and, in children, the lower extremities. Infection starts as an asymptomatic warty papule often mistaken for verruca vulgaris. Slow growth and irregular peripheral extension occur. The lesion may show central involution with an atrophic scar or form massive papillary excrescence with fissures. Pus and keratinous material may extrude from these fissures. Lesions usually are solitary, and regional nodes are not affected unless secondary bacterial infection occurs. Lesions may evolve and persist for years. Spontaneous resolution with scarring can occur.
Histology shows pseudoepitheliomatous hyperplasia with marked hyperkeratosis and a dense inflammatory infiltrate of neutrophils and lymphocytes. Abscesses form in the superficial dermis and epidermis. Epithelioid giant cells occur, but typical tubercles and acid-fast bacilli are rare.
Miliary TB of the skin
Miliary TB of the skin is a rare manifestation of fulminant miliary TB resulting from hematogenous spread of mycobacteria to multiple organs, including skin. The initial site of infection usually is pulmonary or meningeal. This disease occurs predominantly in children and may be coincident with other infections such as measles. Tuberculin sensitivity is absent and bacillary load is high, which is consistent with an overwhelming infection. Currently, numerous instances of miliary TB of the skin are reported in immunosuppressed individuals infected with HIV.[3]
Disseminated lesions occur on all parts of the body, especially the trunk. Lesions erupt as small (millet-sized) red macules or papules. Purpura, vesicles, and central necrosis are common. Histologically, lesions show microabscesses with tissue necrosis and nonspecific inflammatory infiltrates. Tubercle bacilli are numerous and are demonstrated in tissue and intravascular spaces. Affected patients are gravely ill, and the prognosis is poor.
Scrofuloderma
Scrofuloderma results from breakdown of skin overlying a tuberculous focus, usually at a lymph node but also at the skin over infected bones or joints. Historically, a high prevalence of scrofuloderma was seen in children infected with M bovis from contaminated milk. The oral or tonsillar primary lesion progresses to cervical adenitis, formation of cold abscesses, and secondary breakdown of overlying skin.
Lesions present as firm, painless, subcutaneous nodules that gradually enlarge and suppurate and then form ulcers and sinus tracts in overlying skin. Typical ulcers have undermined edges and a floor of granulation tissue. Typical tubercles with acid-fast bacilli are found in the lower dermis and walls of the ulcer or abscess. Tubercle bacilli usually can be isolated from the purulent discharge. Tuberculin sensitivity usually is marked. Spontaneous healing can occur but often takes years and is accompanied by the formation of hypertrophic scars. Lupus vulgaris may develop in the vicinity of healing scrofuloderma.
Metastatic tuberculous abscess (tuberculous gumma) is a variant of scrofuloderma that occurs following hematogenous spread of mycobacteria to skin in tuberculin-sensitive individuals. Painless, fluctuant, subcutaneous abscesses form singly or at multiple sites, then break down into fistulas and ulcers resembling scrofuloderma. Typically, these lesions occur in malnourished children or in severely immunosuppressed patients.
TB cutis orificialis
Orificial TB results from autoinoculation of mycobacteria into the periorificial skin and mucous membranes in patients with advanced TB. Underlying disease can be pulmonary, intestinal, or genitourinary TB. Infectious mycobacteria shed from these foci are inoculated into surrounding mucous membranes and skin. Patients typically are older men. Tuberculin sensitivity is strong. The site of the periorificial lesion often is determined by trauma.
In orificial TB, the tip and lateral margins of the tongue are affected most frequently; however, hard and soft palate lesions also are common. Autoinoculation of tooth sockets can occur after extraction. Perianal skin, the vulva, the urinary meatus, and the glans penis also are described sites. Lesions start as red papules that evolve into painful, soft, punched-out, shallow ulcers. Tubercles with acid-fast bacilli can be found in the deep dermis and ulcer walls. Usually, patients that develop orificial TB have severe internal organ disease and the appearance of these lesions portends a poor prognosis.
Lupus vulgaris
Lupus vulgaris is a chronic and progressive form of cutaneous TB that occurs in tuberculin-sensitive patients. In most series, it is the most common form of cutaneous TB and has the most variable presentation. Lesions appear in normal skin as a result of direct extension of underlying tuberculous foci, of lymphatic or hematogenous spread, after primary inoculation, BCG vaccination, or in scars of old scrofuloderma. Historically, lupus vulgaris was most prevalent in northern Europe (cause of lower prevalence in Asian countries is not known), with affected females outnumbering males by 2-3:1.
Lesions usually are solitary, and more than 90% involve the head and neck. Small, sharply marginated, red-brown papules of gelatinous consistency (apple-jelly nodules) slowly evolve by peripheral extension and central atrophy into large plaques. However, many clinicians in Asian countries who see large numbers of this entity have questioned the descriptive term "apple jelly nodules," since this is not seen in many pigmented patients. Reappearance of new nodules within previously atrophic or scarred lesions is characteristic. Cartilage (nose, ears) within the affected area is progressively destroyed (lupus vorax); bone usually is spared. Buccal, nasal, and conjunctival mucosae may be involved primarily or by extension.
Clinical variants are numerous and are seen in the following forms:
Plaque forms: Disease extension occurs with little central atrophy. Scaling can occur, especially on the lower legs where it may resemble psoriasis. Irregular scarring is common and the active edge may be thickened and hyperkeratotic.
Ulcerating form: Scarring and ulceration predominate. Crusts form over areas of necrosis. Deep tissues and cartilage are invaded by eventual scarring that produces contractures and deformity.
Vegetative form: This form is characterized by necrosis, ulceration, and proliferative and papillomatous granulation tissue.
Nodular form: This form is characterized by a relative absence of ulceration and scarring. Large soft tumors occur, especially on ear lobes.
Histologically, the most prominent feature is a typical granulomatous tubercle with epithelioid cells, Langhans giant cells, and a mononuclear infiltrate. Caseation necrosis is minimal, and acid-fast bacilli are rare. Tissue histology varies with secondary changes of abscess formation, ulceration, atrophy, and scarring.
Lesions often persist for years before diagnosis and can be disfiguring. Patients with lupus vulgaris and pulmonary TB have a 4- to 10-fold higher mortality than with pulmonary TB alone. In long-standing lupus vulgaris, squamous cell carcinoma can occur and be confused with the disease itself.
Tuberculids: Tuberculids are symmetric generalized exanthems in the skin of tuberculous patients, possibly resulting from hypersensitivity reactions to tubercle bacillus. Typically, patients with tuberculids are in relatively good health and show (1) positive tuberculin sensitivity, (2) tuberculous involvement (usually inactive) of viscera or lymph nodes, (3) negative staining and culture for pathogenic mycobacteria in affected tissue, and (4) skin lesions that heal with remission or treatment of TB. Originally, these exanthems were believed secondary to mycobacterial "toxins"; however, recent opinion and identification of mycobacterial DNA by PCR amplification reactions in affected tissue suggest that they are manifestations of hematogenous spread of bacilli in patients with tuberculin immunity.
Erythema induratum (Bazin disease)
Erythema induratum is a persistent or recurring condition associated with past or active TB. Inflammatory cutaneous and subcutaneous nodules that may ulcerate and scar occur in the posterior calves of women's legs (< 10% of affected patients are men). Preexisting erythrocyanotic circulatory disease may predispose patients to lesions. Cutis marmorata is common, and an increased prevalence is seen during cold weather.
Lesions arise in small numbers as tender indurated plaques and nodules that may progress to ulceration and scarring. In early stages, inflammation occurs in venous walls with adventitial thickening and endothelial proliferation. A perivascular inflammatory infiltrate also may be present. Septal panniculitis is present, which may extend into fat lobules. Fat necrosis and foreign-body giant cells occur, and fibrosis and atrophy (Wucher atrophy) replace subcutaneous fat. Tubercle bacilli are not seen, and mycobacterial cultures usually are negative. Erythema induratum often recurs for years.
Papulonecrotic tuberculid
Papulonecrotic tuberculid occurs as a chronic and recurrent symmetric eruption of necrotizing skin papules appearing in clusters and healing with varioliform scars. Tubercle bacilli are difficult to demonstrate, but patients usually have an internal focus of TB and are tuberculin sensitive, and skin lesions resolve after anti-TB therapy. Recent studies detected TB DNA in these lesions using PCR amplification reactions.
Lesions appear on the exterior aspects of extremities (knees, elbows, buttocks, lower trunk) in a symmetric distribution, often in clusters. Individual lesions are asymptomatic, small, dusky red papules with a central punctum or crust. Involution is common after 6-8 weeks and leaves pitted scars.
Histologically, these lesions show a wedge-shaped necrosis of the upper dermis extending to and involving the epidermis. Epithelioid cells and, infrequently, Langhans giant cells are seen. An obliterative granulomatous vasculitis with fibrin present in vessel walls and lumen is typical.
Lichen scrofulosorum
Lichen scrofulosorum is an eruption of asymptomatic, grouped, closely set, 1-2 mm, perifollicular, lichenoid papules affecting children and young adults with underlying TB. The eruption becomes more extensive for weeks and then slowly regresses for months without scarring. Recurrences are possible. The response to anti-TB drugs is not as remarkable as that seen in other tuberculids.
Histologically, tuberculoid granulomas can be seen surrounding hair follicles and sweat ducts. Caseation necrosis usually is absent. No acid-fast bacilli are seen.
Workup for cutaneous TB forms is directed against the underlying systemic disease.
Obtain a medical history for symptoms of the disease, TB exposure or infection, past TB treatment, demographic risk factors for TB, and medical conditions that increase risk for TB.
Obtain specimens for bacteriologic examination: 3 sputum specimens on each of 3 consecutive days.
Alternatively, obtain specimens for histologic examination: acid-fast bacilli in stained tissue or nucleic acid amplification of bacterial DNA and RNA.
Isolate patients with possible TB infection in a private room with negative pressure (air exhausted to outside or through a high-efficiency particulate air filter). Medical staff must wear high-efficiency disposable masks sufficient to filter the tubercle bacillus. Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 wk of treatment). Unfortunately, these measures are neither possible nor practical in countries where TB is a public health problem.
Treatment regimens adequate for pulmonary TB also are effective for extrapulmonary disease. Treat infants and children with miliary TB, bone or joint TB, or TB meningitis for a minimum of 12 weeks.
Because of increased drug resistance among TB isolates, TB treatment regimens must contain multiple drugs to which the isolated bacillus is susceptible. These regimens must be taken regularly and for a sufficient period.
In most patients, initiate anti-TB treatment with a 4-drug regimen and include ethambutol or streptomycin in the initial regimen until results of drug susceptibility are known or the chance of drug resistance is minimized. Low risk of drug resistance may be indicated as (1) less than 4% primary drug resistance to isoniazid in the local community, (2) the patient has had no previous treatment with TB drugs, (3) the patient is not from a country with high prevalence of drug-resistant TB, and (4) the patient has no known exposure to a person with drug-resistant TB.
Short-course therapy (for drug-susceptible strains in HIV-seronegative patients) lasts for 6 months.
The initial phase of 4-drug treatment is for 2 months. The drugs are used as follows:
Isoniazid: 5 mg/kg/d in adults; 10-20 mg/kg/d in children, not to exceed 300 mg qd
Rifampin: 10 mg/kg/d in adults; 10-20 mg/kg/d in children, not to exceed 600 mg qd
Pyrazinamide: 15-30 mg/kg/d in adults and children, not to exceed 2000 mg qd
Ethambutol: 15-25 mg/kg/d in adults and children or streptomycin: 15 mg/kg/d in adults; 20-40 mg/kg/d in children, not to exceed 1000 mg qd
If TB isolates are susceptible to isoniazid and rifampin, the second phase of treatment consists of isoniazid and rifampin for 4 months.
Consider directly observed therapy (DOT) for patients with active disease. This intermittent treatment under direct observation significantly increases cure rate, decreases transmission of disease, and prevents emergence of multidrug resistant TB. DOT has been designed to prevent irregularity in drug intake in TB patients.
The 4-drug DOT administered daily for 2 months can be followed by treatment with isoniazid and rifampin administered 2 or 3 times per week.
Four-drug DOT can be administered daily for 2 weeks, then 2 times per week for 6 weeks, followed by isoniazid and rifampin alone 2 times per week for 16 weeks.
Four-drug DOT can be administered 3 times per week throughout the 6-month treatment period.
Treat drug-resistant strains of tubercle bacilli in consultation with experienced physicians. Additional anti-TB drugs and longer treatment intervals often are needed. Daily DOT is recommended.
Drugs used for this variant include kanamycin, amikacin, capreomycin, ciprofloxacin, ofloxacin, sparfloxacin, ethionamide, and prothionamide.
The role of surgery in cutaneous TB is limited. However, hypertrophic and verrucous lesions of lupus vulgaris and TB verrucosa cutis have been treated with electrosurgery, cryosurgery, and curettage with electrodesiccation as an adjunct measure, with pharmacologic therapy as the primary method of treatment.
Clinical Context:
Has best efficacy, toxicity, and cost profiles. Mechanism of action is not known. INH is bactericidal to both extracellular and intracellular tubercle bacilli.
Clinical Context:
For use in combination with a minimum of 1 other anti-TB drug; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 months or until 6 months have elapsed from conversion to sputum culture negativity. Bactericidal to tubercle bacillus.
Clinical Context:
Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against M tuberculosis, depending on concentration of drug attained at site of infection. Mechanism of action is unknown. Administer for initial 2 mo of 6-mo or longer treatment regimen for drug-susceptible patients. Treat drug-resistant patients with individualized regimens.
Clinical Context:
Bacteriostatic agent to both extracellular and intracellular tubercle bacilli. Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell metabolism by inhibiting synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance demonstrated.
Clinical Context:
For treatment of susceptible mycobacterial infections. Use in combination with other anti-TB drugs (eg, isoniazid, ethambutol, rifampin). Total period of treatment for TB is a minimum of 1 year; however, indications for terminating streptomycin therapy may occur at any time. Recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Strict control of infected patients is essential to treat the infected individual and to prevent disease transmission. The most recent guidelines are outlined by the Centers for Disease Control, Atlanta, GA in the Core Curriculum on Tuberculosis.[4]
Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th ed. Washington, DC: US Dept of Health and Human Services; 2000.
Tappeiner G, Wolff K. Tuberculosis and other mycobacterial infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in General Medicine. 4th ed. New York, NY: McGraw-Hill; 1993:2370-95.
