Cutaneous tuberculosis was a major problem in the late 19th and early 20th centuries. The incidence of cutaneous tuberculosis declined with the decline of pulmonary tuberculosis. Pulmonary tuberculosis declined because of improved hygiene, improved living standards, use of BCG immunization, and the introduction of effective chemotherapy.[1–3] Extrapulmonary tuberculosis constitutes approximately 10% of all cases of tuberculosis and cutaneous tuberculosis makes up only a small proportion of these cases.[4] Based on a study in northern India,[4] 0.1% of patients with a dermatologic disorder had cutaneous tuberculosis, and this percentage is even less in developed countries.[5] In developed countries, cutaneous tuberculosis has typically been observed in those patients with immunosuppression from malnutrition, cancer, chronic corticosteroid therapy, or immunosuppressive therapy, whereas in developing countries it occurs more often in the healthy population.[5] In recent years, however, there has been a resurgence of cutaneous tuberculosis in areas with a high prevalence of HIV infection and multi-drug resistant pulmonary tuberculosis.[3] Because of the rapid pandemic spread of HIV infection, physicians will encounter more cases of cutaneous tuberculosis, particularly the disseminated miliary variant. The ability to recognize tuberculosis of the skin will aid in the rapid diagnosis and timely implementation of therapy.

1. Pathogenesis

Tuberculosis involving the skin is caused by Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine, an attenuated strain of M. bovis.[6,7] These are acid-fast bacilli (AFB) of relatively low pathogenicity that usually require some degree of immune impairment in the host for the development of disease. The development of cutaneous tuberculosis is dictated by the pathogenicity of the infecting organism, the route of infection, the patient’s prior sensitization to tuberculosis, and the nature of the patient’s cell-mediated immunity.[8–10]

2. Classification

The early classification systems for cutaneous tuberculosis were based primarily on the morphology of the skin lesions. As knowledge of the pathogenesis of the disease increased, it became apparent that various forms of cutaneous tuberculosis, though appearing clinically similar, differed in their development, their progression, and their prognosis.

True cutaneous tuberculosis skin lesions show a spectrum of morphological presentations that are characterized by granulomatous inflammation, variable necrosis and variable vasculitis with demonstration of M. tuberculosis by special staining, culture or polymerase chain reaction (PCR).[11] These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid.

The tuberculids, like true cutaneous tuberculosis, also show a spectrum of morphological presentations characterized by granulomatous inflammation, variable necrosis and variable vasculitis. However, unlike true cutaneous tuberculosis, M. tuberculosis is not demonstrated by special staining, culture, or by PCR. While mycobacterium have not been isolated from tuberculid lesions, there is evidence to suggest that M. tuberculosis is an etiologic factor. The tuberculids include lichen scrofulosorum, erythema induratum of Bazin, some cases of papulonecrotic tuberculid, and the recently identified nodular granulomatous phlebitis.[12]

New information has allowed further classification of true cutaneous tuberculosis based on the route of infection and the immune status of the patient. The system proposed by Tappeiner and Wolff uses this new approach.[9] Under this system, true cutaneous tuberculosis is classified as being acquired either exogenously or endogenously. Exogenous infection occurs following the direct inoculation of the organism into the skin of an individual who is susceptible. This includes tuberculous chancre and tuberculosis verrucosa cutis (table I). Endogenous infection (table II) occurs in patients who were previously infected, either by contiguous extension, hematogenous spread, or lymphatic spread. Contiguous extension from an underlying focus appears clinically as scrofuloderma and orificial tuberculosis. Hematogenous spread appears usually as acute miliary tuberculosis, metastatic tuberculous abscess (gummatous tuberculosis), papulonecrotic tuberculid and lupus vulgaris; lymphatic spread is seen occasionally in lupus vulgaris (table II). While this classification system is very useful for the purpose of understanding the many different variant forms of true cutaneous tuberculosis, there is no tight compartment limiting the labeling to either endogenous or exogenous. For example, lupus vulgaris lesions usually originate from an endogenous source of infection but less commonly can be acquired exogenously. Lupus vulgaris can also develop around the sinuses of scrofuloderma or even in tuberculid lesions, thus crossing between the categories of true cutaneous tuberculosis and the tuberculids. Even within the category of endogenously acquired cutaneous tuberculosis, a lesion can be part like lupus vulgaris and part like verrucosa cutis.

Table I
figure Tab1

True cutaneous tuberculosis: exogenous infection

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Table II
figure Tab2

True cutaneous tuberculosis: endogenous infection

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3. True Cutaneous Tuberculosis

3.1 Exogenously Acquired Disease

3.1.1 Tuberculous Chancre

Tuberculous chancre (primary inoculation tuberculosis) develops following the inoculation of M. tuberculosis into the skin of an individual who is nonsensitized.[9,10] The patient is initially purified protein derivative (PPD)—negative, but converts to PPD-positive later in the course of the disease. For infection to occur, there must be trauma to the skin, which creates entry points for the organism. However, in many cases obvious trauma is absent. Usually the trauma occurs through unnoticed abrasions and injuries on the face or limbs.[9,13] Tuberculous chancres have been reported following mouth-to-mouth resuscitation,[14] jail-house tattooing,[15] circumcision, ear and nose piercing,[3] and in healthcare workers.[13] In addition, a case of primary inoculation tuberculosis was reported after immunotherapy for malignant melanoma with BCG vaccine.[16]

Two to 4 weeks following inoculation, an unremarkable reddish-brown papulonodular lesion forms, which rapidly enlarges and erodes. The result is a painless, well demarcated ulceration, with an indurated granular base and edges which may be red, blue, and undermined,[3] and sometimes studded with pustules (figure 1). The tuberculous chancre, along with the associated painless regional adenopathy, constitutes the primary tuberculous complex of the skin, and may represent the cutaneous counterpart of primary pulmonary tuberculosis, the Ghon complex.

Fig. 1
figure 1

Tuberculous chancre.

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The diagnosis can be made by demonstrating AFB on histology sections or smears taken from the ulcer. It is confirmed by a positive culture for AFB. The early histologic changes are those of an acute inflammatory reaction, with areas of necrosis showing numerous tubercle bacilli.[17] After 3 to 6 weeks, the lesion assumes a more granulomatous appearance, showing increased numbers of giant cells and epithelioid cells and decreased number of identifiable tubercle bacilli.[15] This decrease in tubercle bacilli corresponds to the conversion of the tuberculin skin test from negative to positive.[13,17]

Since tuberculous chancre occurs in patients who are nonsensitized, BCG vaccination would serve to sensitize and hence protect the patient. Without antituberculous medications, the primary lesion heals with scarring after several months, and may occasionally evolve into tuberculosis verrucosa cutis or lupus vulgaris. Scrofuloderma may form if regional lymph nodes break down and cause contiguous extension to the overlying skin.[3]

3.1.2 Tuberculosis Verrucosa Cutis

Tuberculosis verrucosa cutis is a form of cutaneous tuberculosis that develops following the inoculation of M. tuberculosis into the skin of a patient who was previously sensitized with an intact immune system; therefore, a patient who is BCG-sensitized is not protected. The tuberculin skin test is usually markedly positive. The inoculation of mycobacteria occurs at sites of skin trauma and is acquired usually through accidental infection while handling either patients with tuberculosis or their autopsy material.[18] This explains the traditional occurrence of this form of tuberculosis in physicians, pathologists (‘anatomist’s warts’), medical students and postmortem attendants (‘prosector’s warts’). Common sites of involvement include the hands, feet and buttocks. Rarely, it is acquired through autoinoculation of a wound with the patient’s own tuberculous sputum.[9,10]

The initial tuberculosis verrucosa cutis lesion is usually a solitary, asymptomatic, slow-growing red-brown papule. It enlarges to form a verrucous plaque resembling a common wart with clefts and fissures of its surface (figure 2). The periphery is firm but the center is soft, and may express pus and keratinous material from its fissures. Normally, there is adenopathy only if the lesion becomes secondarily infected.[9]

Fig. 2
figure 2

Tuberculosis verrucosa cutis.

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Culture of a skin biopsy specimen may be helpful in making a diagnosis, but it is usually negative because of the high degree of antituberculosis immunity in patients who develop tuberculosis verrucosa cutis.[19] The diagnosis may be made through histology. Examination of biopsy material shows hyperkeratosis and papillomatosis of the epidermis. The dermis contains tuberculoid granulomas with moderate necrosis and occasional AFB.[17] These lesions persist for many years, but may spontaneously regress without therapy, leaving behind atrophic scars.[9]

3.2 Endogenous Infection

3.2.1 Lupus Vulgaris

Lupus vulgaris usually originates from an endogenous source of tuberculosis and is spread hematogenously, lymphatically, or by contiguous extension. Less commonly, it is acquired exogenously following primary inoculation tuberculosis or BCG vaccination.[9] Lupus vulgaris occurs in individuals with a variable degree of immunity who demonstrate marked tuberculin sensitivity. Therefore, it is unclear whether BCG vaccination is protective or not. Lupus vulgaris is generally regarded as a benign, chronic and progressive form of cutaneous tuberculosis that may be associated simultaneously with tuberculosis of other organs. Marcoval et al. cite that 9 to 19% of patients with lupus vulgaris of the skin have simultaneous tuberculosis elsewhere.[20] If the PPD is negative in a patient known to have lupus vulgaris, visceral involvement causing diminished delayed hypersensitivity reaction should be ruled out.[20] Lupus vulgaris is the most common type of cutaneous tuberculosis in Europe, though the overall incidence has declined steadily.[20] It is now also the most common type of true cutaneous tuberculosis in Hong Kong, whereas in the past it was tuberculosis verrucosa cutis.[5]

The lesions of lupus vulgaris typically arise on the head and neck area in Western countries, in which case there may be involvement of the mucous membranes. The lower extremities and buttocks are most often involved in the tropics and subtropics.[3] Lupus vulgaris has several discrete clinical presentations. Four types of lesions predominate: plaque, hypertrophic, ulcerative and vegetative forms. The plaque-type lesion starts as a brown-red discoloration, which becomes infiltrated to form a brown-red papule or serpiginous plaque of almost gelatinous consistency. Scale may or may not be present (figure 3). The lesion extends peripherally, leaving behind an atrophic scar, from which new lesions may develop. Pressing on the lesion with a glass slide may display the characteristic ‘apple-jelly’ color which is often not appreciated in people with darker skin, where this entity is seen more often. The hypertrophic form displays soft tumor nodules, and is deeply infiltrating. In the ulcerative form, the underlying tissue becomes necrotic and breaks down. This may result in marked destruction, particularly if auricular or nasal cartilage is involved. The vegetative form consists of papular and nodular forms, and is marked by necrosis and ulceration; there is minimal scarring.[3]

Fig. 3
figure 3

Lupus vulgaris.

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The histologic examination shows typical tuberculoid granuloma with occasional areas of caseation necrosis, particularly in the upper dermis.[17] Tubercle bacilli are sparse and therefore not frequently seen. The diagnosis may be confirmed on culture, though the yield is quite low. Because of the relatively high frequency of clinically inapparent simultaneous visceral involvement, treatment consists of standard multiple drug antituberculous medications in order to prevent recurrence of tuberculosis. Complications related to the long term sequelae of untreated lupus vulgaris include marked contractures, scarring, and the development of carcinomas and sarcomas.[9,10,21]

3.2.2 Scrofuloderma

Scrofuloderma results from contiguous extension of an underlying tuberculous focus secondary to local tissue breakdown. The underlying focus may be a tuberculous bone or joint or even epididymis, but it occurs most commonly over a lymph node, particularly the cervical lymph node.[3,22] Often, it is associated with tuberculosis elsewhere, especially of the lungs. In developing countries, consumption of unpasteurized milk containing M. bovis is a common source of infection causing scrofuloderma, especially in the cervical region.[22] Scrofuloderma starts as a red-brown deep nodule overlying an affected lymph node, which becomes indurated and then breaks down (figure 4). The resulting ulcers and sinuses may drain watery, purulent, or caseous material.[22]

Fig. 4
figure 4

Scrofuloderma.

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Diagnosis is easily made by culture, biopsy, smear for demonstration of AFB or less commonly by guinea pig inoculation. Tubercle bacilli are usually easy to identify in the purulent discharge or biopsy tissue. Histologically, the site of granuloma formation is the lower dermis. The periphery of the lesion contains tuberculoid granulomas with caseation necrosis and pronounced inflammation; centrally, there is necrosis, corresponding with the ulceration that is seen clinically.[17] Scrofuloderma may heal spontaneously, but this may take years.[9,10]

3.2.3 Acute Disseminated Miliary Tuberculosis

Disseminated miliary tuberculosis (Tuberculosis Cutis Miliaris Acuta Generalisata) of the skin, once a rare form of tuberculosis that occurred mainly in infants in the prechemotherapy era, has now re-emerged among patients infected with HIV. From the turn of the century until 1991, only 25 cases of disseminated miliary tuberculosis of the skin were reported in adults worldwide; however, in the last 10 years this unusual presentation of tuberculosis has been reported in at least 15 patients infected with HIV.[23]

Disseminated miliary tuberculosis is spread via the bloodstream from an internal focus of active tuberculosis, usually pulmonary.[3] While the PPD is occasionally positive, it is usually negative because of anergy.[9,10] Because disseminated miliary tuberculosis may follow viral exanthemas, this form of tuberculosis should be considered in the differential diagnosis of a patient with tuberculosis who manifests an unusual exanthematous rash.[3] Stack et al.[24] reported the first case of miliary tuberculosis presenting as skin lesions in a patient with AIDS in 1990. A second case was reported by Rohatgi et al.[25] in 1992, who noted that cutaneous involvement is rare in acute miliary tuberculosis in people not infected with HIV.

Clinically, acute disseminated miliary tuberculosis is marked by profuse discreet pinpoint purpuric papules topped with minute vesicles. The vesicles eventually rupture or dry, forming a crust with umbilication. The lesion may heal, usually within 1 to 4 weeks, as a white depressed scar, with a brownish halo.[3]

Diagnosis is confirmed by biopsy, which almost always reveals numerous AFB, microabscesses, and nonspecific inflammation.[17] Therefore, it is important to perform skin biopsies for all HIV-infected patients with papulopustular eruptions and routinely send the specimens for microscopic examination and cultures. Detection of M. tuberculosis DNA by PCR may be used in situations where a diagnosis is made retrospectively or cultures are not performed.

All patients with HIV who have acute disseminated miliary tuberculosis have advanced AIDS, as reflected by severe CD4+ T cell depletion (<100 mm3) and the occurrence of AIDS-defining conditions. The combination of an inadequate immune response and lack of effective antituberculous treatment contributes to the hematogenous dissemination of the infection to many organs, including the skin.[23] In most of these patients, tuberculosis is caused by multi-drug resistant organisms and the outcome is universally fatal. In the rare cases of those patients with HIV with susceptible M. tuberculosis infection, the outcome was good when isoniazid-based combination therapy was initiated promptly.[26,27] With the increased prevalence of HIV disease throughout the world and the accelerated transmission of tuberculosis and multi-drug resistant organisms amongst patients with HIV, more cases of the once rare condition are likely to be encountered by healthcare providers in the future.

3.2.4 Orificial Tuberculosis

Orificial tuberculosis (tuberculosis cutis orificialis) is a rare condition that may occur in patients with advanced tuberculosis of the lungs, intestine, or genito-urinary tract. In such patients, the mucosa and orificial skin (nose, mouth, anus) become infected when mycobacteria are introduced by autoinoculation from sites draining active tuberculosis infection. Hematogenous or lymphatic dissemination from another active source of tuberculosis sometimes occurs.[22] Some patients are PPD-positive, but most are anergic as a result of their impaired cell-mediated immunity.

Clinically, edematous reddish or yellowish nodules appear on the lips, inside the mouth, or on the anogenital area. These nodules rapidly break down to form painful circular or irregular ulcers with undermined edges, a soft consistency, and often a typical ‘punched-out’ appearance (figure 5).[22] In the mouth, the tongue is most frequently affected but the soft and hard palate, and in far advanced cases, the lips, may also be involved. Oral involvement often represents extension of tuberculosis from the pharynx and larynx. Anal involvement occurs in cases of intestinal tuberculosis and vulvar involvement in females with active genitourinary disease.[9]

Fig. 5
figure 5

Orificial tuberculosis.

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The diagnosis can be suspected because it occurs in patients with evidence of tuberculosis elsewhere, but it is confirmed when AFB are demonstrated on histology. The biopsy shows an ulcer surrounded by nonspecific inflammation in the upper sections, and caseating granuloma in the deep dermis.[17] Orificial tuberculosis is a marker of advanced internal disease and portends a poor prognosis, even if antituberculous therapy is instituted. The lesions do not usually respond to treatment.[22]

3.2.5 Gummatous Tuberculosis

Gummatous tuberculosis (metastatic tuberculous abscess) is due to hematogenous spread of mycobacteria from a primary focus during a period of lowered resistance. It usually occurs in undernourished children or patients who are severely immunosuppressed. Non-tender and fluctuant subcutaneous abscesses may arise as single or multiple lesions on the trunk, extremities, or head. The lesions often invade the overlying skin and break down, forming lesions indistinguishable from scrofuloderma.[12] This condition may occur with progressive organ tuberculosis but may also occur without any underlying tuberculous source. As in scrofuloderma, massive necrosis and abscess formation are found on histology. Acid-fast stains usually reveal large amounts of mycobacteria.[9,12]

3.2.6 Papulonecrotic Tuberculid

With the advent of PCR detection of M. tuberculosis DNA in papulonecrotic tuberculid lesions,[28] most cases of this condition are considered true cutaneous tuberculosis; however, some cases are considered tuberculids. Papulonecrotic tuberculid typically afflicts children and young adults. The tuberculin test is positive in most cases, and usually there is evidence of tuberculous lymphadenitis. These patients develop symmetrical, asymptomatic crops of dusky red pea-sized papules primarily on the extensor aspects of the arms and legs, especially around the elbows and knees, but other areas are sometimes affected. The papules are often crusted or ulcerated and there may be pustules present. These lesions spontaneously involute, leaving many pitted scars (figure 6). The presence of active lesions adjacent to areas of scarring is considered a diagnostic aid to papulonecrotic tuberculid.[29]

Fig. 6
figure 6

Papulonecrotic tuberculid.

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Interestingly, Jordaan et al.[30] state that papulonecrotic tuberculid has been associated with Takayasu’s arteritis; they suggest that there may be a tuberculosis etiology to some forms of arteritis.[30,31] They speculate that perhaps papulonecrotic tuberculid is the result of mycobacterial products lodging in small, superficial vessels and erythema induratum forms if the products lodge in larger, deeper vessels.[29]

As a rule, tubercle bacilli are not seen on tissue examination and cannot be cultured[9,10] but in many cases DNA has been detected by PCR.[28] Histologically, there is usually a wedge-shaped area of necrosis involving the upper dermis and epidermis, and there may be a leukocytoclastic vasculitis or granulomatous infiltrate present.[30] The lesions respond dramatically to antituberculous therapy.[30]

4. Tuberculids

The exact relationship between tuberculosis and tuberculids is poorly understood. The term ‘tuberculid’ has undergone evolution in its definition. In 1896, the term tuberculid was used by Darier to denote recurrent papular and nodular skin eruptions with a tendency to spontaneous involution, induced from toxins of tubercle bacilli.[32] Today, the term refers to conditions in which reasonable evidence exists to support a M. tuberculosis etiology. Such evidence includes strong PPD reactivity and response of lesions to antituberculosis medications (table III). In addition, even though culture and special stains have failed to reveal M. tuberculosis in tuberculid skin lesions,[29] when the incidence of tuberculosis declined, so too did the incidence of tuberculids.[9]

Table III
figure Tab3

The tuberculids

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Histologically, all tuberculids display granulomatous inflammation, variable necrosis and variable vasculitis. Some feel that tuberculids may be a hypersensitivity reaction to M. tuberculosis after it spreads hematogenously from a focus of infection elsewhere.[29]

Tuberculids may be thought of as belonging to either one of two groups: the true tuberculids or the facultative tuberculids. The ‘true tuberculids’ are papulonecrotic tuberculid and lichen scrofulosorum, and are deemed such because M. tuberculosis appears to play a significant etiologic role. For instance, papulonecrotic tuberculid lesions may give rise to lupus vulgaris from which M. tuberculosis has been cultured, and this lends strong support for a tuberculous origin of a tuberculid.[30] Therefore, many cases of papulonecrotic tuberculid are actually considered true cutaneous tuberculosis. The ‘facultative’ tuberculid is erythema induratum of Bazin; this represents a condition where M. tuberculosis is one of several etiologic agents.[9]

4.1 Lichen Scrofulosorum

Lichen scrofulosorum occurs most commonly in children with tuberculosis. The tuberculin test is usually positive, and is most frequently associated with chronic tuberculosis of the lymph nodes and bones.[33] Clinically, there are numerous asymptomatic tiny perifollicular grayish-white lichenoid papules arranged in groups, distributed on the trunk (figure 7). Superficial dermal granulomas without evidence of caseation necrosis develop around hair follicles or sweat ducts.[17] No mycobacteria are found on histologic sections, nor can they be cultured. The lesions will resolve spontaneously after several months to several years without scarring, but will also respond to antituberculous therapy.[34]

Fig. 7
figure 7

Papules of lichen scrofulosorum.

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4.2 Erythema Induratum of Bazin

Originally described by Ernest Bazin in 1861,[35] erythema induratum of Bazin is a common tuberculid with an overwhelming female preponderance. It describes the indurated, often ulcerated erythrocyanotic, nodules that arise on the calves, especially the posterolateral aspect, of those with heavy legs (figure 8). Less frequently, it may occur on the thighs and upper extremities or men may be affected.[36] Recurrences, particularly during the colder seasons, are common. In Hong Kong, it is the most common form of cutaneous tuberculosis, with a continuous rise in its occurrence since 1968.[5] Patients display tuberculin hypersensitivity[35] but active tuberculosis is only rarely identified.

Fig. 8
figure 8

Erythema induratum.

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The histologic changes of erythema induratum include inflammation of the subcutaneous fat lobules, vasculitis, and tuberculoid granulomas with caseation necrosis.[14] The lesions resolve slowly, even in the presence of antituberculous therapy.

Although a causal relationship between erythema induratum and M. tuberculosis remained elusive for many years because of the absence of demonstrable organisms in skin lesions, a recent study showed identification of organism DNA by PCR of biopsy lesions.[35] As the technology available to identify M. tuberculosis organisms becomes more sophisticated, the very criterion that has served to distinguish true cutaneous tuberculosis from the tuberculids is no longer a clear-cut classification tool.

4.3 Nodular Granulomatous Phlebitis

Nodular granulomatous phlebitis (phlebitic tuberculid) is a recently identified, uncommon tuberculid that occurs in patients hypersensitive to tuberculid but without active tuberculosis.[37] Clinically, nonulcerating, subcutaneous nodules are located along the leg veins of the anterior and medial side of the leg. This contrasts with erythema induratum of Bazin, where indurated nodules may ulcerate and have a predilection for the calves.[36]

Histologically, epithelioid cell granulomas with Langerhan’s giant cells are found in the walls of cutaneous veins. Using PCR, M. tuberculosis DNA was detected in four of the five cases of nodular granulomatous phlebitis first reported.[37] This condition seems to represent an early phase hypersensitivity reaction to M. tuberculosis and is likely a distinct entity different from other types of tuberculid.

5. Current Methods for Diagnosis

Diagnosing cutaneous tuberculosis may be a formidable task. The history, clinical presentation, PPD, and histology (including smear for demonstration of AFB) may be suspicious for a diagnosis of tuberculosis, but the definitive diagnosis can only be made by isolating M. tuberculosis on culture. However, the sensitivity for isolating M. tuberculosis on culture is often low, due in part to the presence of scanty or nonviable mycobacteria.[3] When enough viable mycobacteria are present, culture with subsequent identification of isolates may take up to 6 to 8 weeks or longer; mycobacterial growths that appear on Lowenstein-Jensen medium within several days are atypical mycobacteria.

Smear for demonstration of AFB is particularly helpful in lesions with a high bacillary load such as disseminated miliary tuberculosis, scrofuloderma and gummatous tuberculosis lesions.[23] Guinea pig inoculation has also been used to isolate M. tuberculosis from suspicious skin lesions, including two cases of erythema induratum of Bazin.[35] No correlation has been found between Mantoux reactivity and the extent of cutaneous tuberculosis disease (localized vs disseminated).[12]

Recently, PCR has been developed for rapidly identifying organisms such as M. tuberculosis. By utilizing even minute amounts of tissue, specific DNA sequences may be amplified in vitro. Together with various primer/probe systems, a high degree of sensitivity and specificity is obtained for identifying and differentiating mycobacterial species. It is expected that PCR will prove to be valuable in examining granulomatous and tuberculid lesions for M. tuberculosis and will therefore aid the prompt institution of therapy, as well as help delineate the multitude of diseases that mycobacteria cause.[11] PCR has already been utilized to identify M. tuberculosis in lesions of lupus vulgaris, scrofuloderma,[38] as well as nodular granulomatous phlebitis[37] and papulonecrotic tuberculids.[39]

6. Treatment

The optimal treatment for cutaneous tuberculosis consists of a multiple drug regimen for a duration that is long enough to kill all viable organisms, thus preventing the emergence of resistant strains and recurrences. Since most patients with cutaneous tuberculosis have systemic disease involvement as well, the treatment of tuberculosis of the skin is that of tuberculosis in general.[9] It is inferred that antituberculosis regimens used for pulmonary tuberculosis are adequate for treating cutaneous tuberculosis because the bacillary load in cutaneous tuberculosis is usually much smaller than in pulmonary tuberculosis.[19]

The Centers for Disease Control and Prevention recommends chemotherapy that is split into two phases.[40] The initial intensive phase, which consists of daily isoniazid, rifampin, pyrazinamide and either ethambutol or streptomycin for 8 weeks, is directed at rapidly destroying large numbers of viable organisms. Ethambutol or streptomycin are discontinued if mycobacteria prove susceptible to isoniazid and rifampin or in areas where isoniazid resistance is less than 4%. The maintenance or continuation phase, which consists of isoniazid and rifampin given daily, three times weekly or twice weekly for 16 weeks, is directed at eliminating the remaining, persistent organisms. Three times weekly or twice weekly therapy is reserved for directly observed treatment as occurs in healthcare institutions or prisons.[9]

There are some special considerations in the therapy of cutaneous tuberculosis. Reported cases of cutaneous tuberculosis resulting from accidental inoculation by otherwise healthy laboratory personnel have shown successful resolution of lesions as quickly as 3 months with a course of isoniazid, rifampin and ethambutol.[41] However, since viable mycobacteria have been cultured from clinically healed lesions, treatment should be continued for at least 2 months after complete involution of lesions.[9]

Surgical excision is sometimes necessary as an adjunct to chemotherapy, especially in the management of scrofuloderma and localized lesions of tuberculosis verrucosa cutis and lupus vulgaris.[9] Cryotherapy or electrocautery may be used to destroy lupoid nodules that are within scarred areas.[3]

Prevention of cutaneous tuberculosis may be provided by the BCG vaccine where patients with disseminated disease are less likely to have been BCG vaccinated than those with localized disease. One study showed more unvaccinated individuals in a group with disseminated types of cutaneous tuberculosis (80.3%) than those with localized cutaneous tuberculosis (65.5%).[12] However, there are examples of diseases, such as tuberculosis verrucosa cutis, where individuals who were previously BCG-sensitized are actually at risk.

7. Conclusion

Because of the increase of pulmonary tuberculosis infection, particularly in the AIDS era, there has been an increase in the incidence of cutaneous tuberculosis. The diagnosis of cutaneous tuberculosis is easily made if one considers it in the differential diagnosis, particularly in those patients with a history of tuberculosis and a suggestive clinical presentation; otherwise, it is easily missed. Hopefully, this review will aid physicians, especially those caring for patients who are immunosuppressed, when thinking of this diagnosis. By utilizing the appropriate laboratory techniques to identify the organism, the correct diagnosis can be made and the appropriate management can be implemented in a timely fashion, thus minimizing morbidity and mortality.