Cutaneous Tuberculosis



Monte S Meltzer, MD, Chief, Dermatology Service, Union Memorial Hospital

Nothing to disclose.


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.


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).


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]


Disease transmission

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.


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.



United States

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.


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.


Male-to-female ratio is 1.35:1.


Although no age group is exempt, most patients show clinical infection within the first 3 decades of life.


The variants of cutaneous TB present as follows:

Laboratory Studies

Workup for cutaneous TB forms is directed against the underlying systemic disease.

Imaging Studies

Obtain a posteroanterior chest radiograph.

Other Tests

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.


Perform a deep biopsy for suspected lupus vulgaris.

Medical Care

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:

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.

Surgical Care

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.

Medication Summary

The goal of pharmacotherapy is to reduce morbidity and prevent complications.

Class Summary

Inhibit M tuberculosis growth.

Isoniazid (INH, Laniazid)

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.

Rifampin (Rifadin, Rimactane)

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.

Pyrazinamide (PZA, Tebrazid)

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.

Ethambutol (Myambutol)

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.

Streptomycin sulfate

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.

Further Inpatient Care

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]


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