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Anais Brasileiros de Dermatologia

versão impressa ISSN 0365-0596

An. Bras. Dermatol. vol.89 no.6 Rio de Janeiro nov./dez. 2014 


Update on cutaneous tuberculosis*

Maria Fernanda Reis Gavazzoni Dias1 

Fred Bernardes Filho1 

Maria Victória Quaresma1 

Leninha Valério do Nascimento2 

José Augusto da Costa Nery3 

David Rubem Azulay1  4 

1Instituto de Dermatologia Professor Rubem David Azulay - Santa Casa da Misericórdia do Rio de Janeiro (IDPRDA-SCMRJ) - Rio de Janeiro (RJ), Brazil

2Hospital Central do Exército (HCE) - Rio de Janeiro (RJ), Brazil

3Fundação Oswaldo Cruz (FIOCRUZ) - Rio de Janeiro (RJ), Brazil

4Pontifícia Universidade Católica do Rio de Janeiro (PUC-RJ) - Rio de Janeiro (RJ), Brazil


Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction.

Key words: Erythema Induratum; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis; Cutaneous


Tuberculosis (TB) continues to draw special attention from health care professionals and society as a whole. It still meets all the criteria for prioritization of a public health disorder, i.e. large magnitude, vulnerability and transcendence.1 Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin (BCG), which depending on individual immunity, environmental factors and type of inoculum may present varied clinical and evolutionary aspects.2 - 4

Since 2009, the Brazilian Ministry of Health recommends the use of ethambutol as the fourth drug associated with rifampicin, isoniazid and pyrazinamide to treat tuberculosis. It is recommended that cases of cutaneous TB should be discussed within the health unit TB program.1 , 5

The association of TB with HIV infection represents an additional challenge worldwide. An increase in its incidence has been described in several countries in recent years, especially in urban centers and regions with high prevalence of human immunodeficiency virus (HIV) infection.6 Complications related to immune reconstitution induced by antiretroviral therapy, known as immune reconstitution inflammatory syndrome (IRIS) may occur, including paradoxical worsening of cutaneous tuberculosis and the emergence of subclinical infections. The most common clinical presentations of infection by Mycobacterium tuberculosis-associated IRIS are lymphadenitis or lymphadenopathy.7 - 9

Knowledge about TB infection and its clinical management were outside the scope of most dermatological practices. However, the introduction of biologic therapies demanded from dermatologists a deep and up-to-date knowledge of tuberculosis.10

This article provides relevant current information on the definition, epidemiology, recognition of clinical presentation, microbiology and immunology of infectious agents, diagnostic methods and treatment of cutaneous tuberculosis.


According to the World Health Organization (WHO), in 2011, there were about 8.8 million incident cases of TB, 1.1 million deaths from TB among HIV-seronegative persons and an additional 350,000 deaths from HIV-associated TB. In the same year, 84,137 cases of tuberculosis were reported in Brazil, of which, 74,892 were newly diagnosed or retreatment cases and 2,755 were from other causes (unknown history). Amongst the new cases, 56% had positive bacilloscopy, 18% had negative smear, 12% were unknown, 14% were cases of extra pulmonary tuberculosis and 1% of unspecified TB. Regarding cases of retreatment, 35% were due to recurrence, 2% to therapy failure, 33% to abandonment of treatment and 29% to other causes (unknown history).11 Records of TB in Brazil do not specify the cutaneous form, which led to lack of data on its incidence.1 , 5

About 20% of TB cases in children have extrapulmonary presentation. The most common forms are: peripheral lymphadenopathy, pleural, bone and meningoencephalic TB.12

According to the Ministry of Health (MH), in 2011, the Brazilian states that reported most cases of TB were Sao Paulo (16,630 cases), Rio de Janeiro (11,651), Bahia (5,257) and Rio Grande do Sul (5,031).13


Mycobacterium tuberculosis bacillus, or bacillus Koch (BK) is a transitional form between actinomycetes and eubacteria. It belongs to class Schizomycetes, order Actinomycetales, family Mycobacteriaceae and genus Mycobacterium. Robert Koch first described it on March 24th, 1882. This is a non-spore-forming, nonmotile, non-toxin producer, strictly aerobic bacillus and a facultative intracellular species. It has an extended growth period (16 to 20 hours) and doubling time (18 to 48 hours). These bacilli present acid-alcohol-resistant staining properties - i.e., they stain red by fuchsin and will not discolor by the actions of alcohol and acid, hence the name AFB - Acid-Fast Bacilli. Its genome has already been sequenced.14 - 17

Although it may cause illness in men, M. bovis is considered a zoonotic disease that usually affects tonsils, lymph nodes and intestine. It may rarely be the cause of the cutaneous form of TB. When causing lung disease, M. bovis is not easily transmitted and therefore, there is a tendency for its disappearance.18 , 19

Bacillus Calmette-Guerin (BCG) is a lyophilized vaccine developed in 1908, prepared from a live, attenuated strain of Mycobacterium bovis. Adverse events associated with BCG vaccine are uncommon, but local or systemic complications may occur.20 , 21 They depend on the strain used and are more common amongst infants than adolescents. Ulceration, subcutaneous abscess and suppurative lymphadenitis occur in 0.4 per 1,000 vaccinations, appearing in the first 6 months after vaccination. Hypertrophic and keloid scarring occur in 4 per million vaccinated. Systemic complications and fatal dissemination are rare (<1.5 per million). Although generally safe, vaccine reactions such as skin complications are well known and can include local hypersensitivity reactions, cutaneous granulomas, fixed drug eruption and cutaneous tuberculosis.21 The World Health Organization currently recommends that BCG vaccine should be administered to all those living in areas of endemic tuberculosis. In Brazil, the vaccine is part of the national immunization schedule and according to the MH's immunization manual it is indicated right after birth, as early as possible.22 The interval between vaccination and the development of skin lesions may be of several months or years, with an average duration of 1 year. Factors that may be responsible for the development of BCG reactions include inherent susceptibility of the organism to BCG virulence, to the amount of inoculum and the inoculation technique.21 , 23 , 24


Just as in leprosy and pulmonary tuberculosis, there is a concept of spectrum in cutaneous tuberculosis. Based on bacteriological, histopathological and immunological parameters, Sehgal et al proposed a continuous spectrum extending from the greater cellular immunity pole, observed in lupus vulgaris, with active cellular immunity and apparently normal levels of immunoglobulins, to scrofuloderma and cutaneous miliary tuberculosis, which present a relatively less active cellular immunity and high humoral response, as evidenced by elevated immunoglobulin serum levels and low levels of C3.25 , 26

The introduction of more specific and sensitive diagnostic methods, as well as a greater understanding of the molecular and cellular mechanisms that regulate the parasite-host interaction may contribute to an efficient fight against tuberculosis. Immunosuppression, either due to a poor state of health, HIV infection or to the use of immunosuppressive drugs, represents the main trigger for active disease development, caused by M. tuberculosis. 27

Tissue macrophages constitute one of the first lines of defense against mycobacteria. After being phagocytized, the bacilli remain within the phagosome. After the phagosome-lysosome fusion, antigens can be processed and subsequently presented to Thelper lymphocytes (CD4 +) through major histocompatibility complex (MHC) class II. CD4 + type 1 cells (Th1) play a major role in the immune response to mycobacteria.27 , 28

In the case of mycobacteria, it was demonstrated that apoptotic vesicles, originated from infected cells and containing bacillary antigens associated to MHC class I, are able to specifically stimulate CD8 + T cells also participating in the immune response to M. tuberculosis. 29

CD4- and CD8- lymphocytes with gamma/delta chain polypeptide-containing receptors recognize phosphoric components of M. tuberculosis, regardless of MHC class I or II, whereas T lymphocyte receptors, restricted only to CD1, can be stimulated by glycolipids derived from the mycobacterial wall. Therefore, the immune system is able to recognize and effectively respond to a broad range of antigenic determinants with different biochemical characteristics. In this recognition process, there is a hierarchy among T cell subpopulations that contribute to the immune response to mycobacteria, with CD4 + and CD8 + lymphocytes being the most important cells in this ranking.27 , 30

Regarding the innate immune response, neutrophils are the first inflammatory cells to settle on the bacillary multiplication site, followed by natural killer cells (NK) and macrophages. The recognition and phagocytosis of bacteria by innate immunity cells (neutrophils, macrophages, and dendritic cells) occur via recognition receptors, such as mannose receptor, antibody Fc portion receptors (FcRs) and complement system activation products receptors, as C3b and C4b (CR1), among others. Activation of pattern recognition receptors, such as Toll-like receptors (Toll-like receptors, TLRs), leads to an important link between the innate and acquired immune responses.27 , 31 , 32

Cytokines are a central component in the defense against mycobacteria. At all stages of immune response, produced cytokines participate in the regulatory process, and effector functions. Recognition of mycobacteria and subsequent secretion of IL-12 by macrophages are processes initiated prior to the presentation of M. tuberculosis antigens to T lymphocytes. IL-12 induces the production of interferon gamma (IFN-γ) in NK cells in the initial phase of immune response and also induces the activation, differentiation, IFN-γ production and antigen-specific Th1 cells expansion. Th1 cells are the major source of IL-2 and IFN-γ during acquired immune response and are necessary to control the chronic phase of infection, because of these cytokines' actions on T cells and macrophages. Produced by macrophages and dendritic cells and acting on T cells, IL-12 forms a link between innate and acquired responses. Individuals with mutations in IL-12 p40 and IL-12R genes show a reduced IFN-γ production by T cells and are more susceptible to disseminated infections by Bacillus Calmette-Guerin vaccine (BCG) and M. avium.27 , 28 , 33

Macrophagic bactericidal activity against M. tuberculosis needs to be previously activated and IFN-γ is the main and most potent mediator of this process.34 IFN-γ is able to increase the expression of several genes in the macrophage, induce an increase in MHC expression (increase in antigen presentation) and in immunoglobulin receptors (FcRs and increased capacity for phagocytosis), recruit T lymphocytes involved in destruction of bacteria and participate in the production of nitric oxide. Although the isolated production of IFN-γ is insufficient to control the bacillus, IFN-γ is one of the crucial components of the protective response against the pathogen. IFN-γ, in synergy with tumor necrosis factor alpha (TNF-α), activates infected macrophages, initiating an important effector mechanism of cell-mediated immunity. While the ability to produce IFN-γ can vary among individuals, some studies suggest that the levels of IFN-γ are decreasing in patients with active TB. These levels are even lower in patients with advanced pulmonary disease. Furthermore, it was demonstrated that M. tuberculosis could prevent macrophages from adequately responding to IFN-γ. TNF-α is a proinflammatory cytokine that also plays a central role in the immune response against M. tuberculosis, contributing to granuloma formation, which isolates bacilli and prevents their spread. T-helper lymphocytes, from CD4+ lineage, release IFN-γ and TNF-α, which account for the transformation of macrophages and monocytes into specialized histiocytes with bacteriostatic and bactericidal capacity. This immune response is amplified by TNF-α which modulates the synthesis of IL-12 and NF-kB , promoting the expansion of CD4 + Th1 lineage.35 , 36

Th1 cells mediate immunity against TB. However, it was recently reported that, besides the cytokines produced by Th1 cells, there is also IL-4 production in human TB. IL-4 has the ability to downregulate the expression of TLR2 and macrophage activation. Recently, CD4+ and CD25+ regulatory T cells have been identified. These cells produce IL 10 and transforming growth factor-beta, and are able to express TLRs (which can react with myco¬bacteria) and participate in the suppression of protective immunity. Therefore, they constitute a potentially important factor at the onset of the infection, since they can influence the latency or progression of TB.27


Tuberculin skin test (TST) or Mantoux test is the intradermal inoculation of M. tuberculosis purified protein derivative (PPD) to measure the cellular immune response to these antigens. It was developed by Florence Siebert in 1939 and remains a reference for all tuberculins. PPD components are mostly proteins with molecular weights of approximately 10,000 d, but there are also polysaccharides and some lipids. The relatively small size of PPD protein constituents is the reason why it does not usually sensitize individuals who have not been previously exposed to mycobacteria. When stored at temperatures between 4 and 8ºC, tuberculin remains active for six months. It should not, however, be frozen or exposed to direct sunlight.1 , 37

The tuberculin used in Brazil is PPD RT-23, administered intradermally in the middle third of the left forearm anterior surface, at a dose of 0.1ml, containing 2UT (units of tuberculin), which is biologically equivalent to 5UT of PPD-S used in other countries.1 The application and reading techniques, and materials used are standardized by WHO.38 - 40 Reading should be performed 48 to 72 hours after application and it can be extended to 96 hours if the patient does not attend the scheduled reading date.41 - 43

People with specific antituberculosis cellular immunity develop limited erythema and induration at the site of the tubercle protein intradermal injection, usually peaking within 48 to 72 hours after exposure. This delayed-type hypersensitivity is a result of the influx of lymphocytes that are sensitized to the injected antigen and lymphokines released from these T cells, resulting in vasodilation, local edema and recruitment of other inflammatory cells to the area.44 , 45

Reaction to tuberculin skin test should be measured by the Sokal ballpoint pen technique and the reading recorded in mm of induration.46 The largest transverse diameter of palpable induration area should be measured with a transparent millimetered ruler and the result recorded in millimeters. The isolated classification of TT (Tuberculin Test) in nonreactor, weak reactor and strong reactor is no longer recommended, as the interpretation of the test and its cutoff values may vary according to the population and the disease risk. Individuals with documented TT with results equal to or greater than 10 mm should not be retested. It is necessary to emphasize that the size of reaction in the patient, can guide important therapeutic decisions.1

The tuberculin test can be interpreted as suggestive of M. tuberculosis infection when equal to or greater than 5mm in children not vaccinated with BCG, children vaccinated more than two years before the test was performed or those with any immunosuppressive condition. In children vaccinated less than two years before the test, TT is considered suggestive of infection when equal to or exceeding 10mm.47 , 48

Cellular immunity induced by nontuberculous mycobacteria such as M. scrofulaceum and M. avium complex can cause a cross-reaction induration, usually around 5-10 mm. The aforementioned classification is valid only for patients with negative serologic HIV testing. Individuals infected with HIV are considered infected with TB bacillus when presenting tuberculin test with induration equal to or greater than 5 mm. Another important detail is that tuberculin test may lose its value in individuals vaccinated with BCG in the three years preceding the test date.49 , 50

False-positive reactions may occur in individuals infected with other mycobacteria or vaccinated with BCG, especially if vaccinated (or revaccinated) after the first year of life, when BCG induces stronger and long-lasting reactions. However, the reaction tends to diminish over time and if TT is performed ten years or more after the last vaccination, the effect of BCG on it may be minimal.1 , 43 , 51 - 54 False negative reactions (individuals with latent infection by M. tuberculosis - LTBI and negative tuberculin test) may occur in the circumstances depicted on chart 1.53 , 54

CHART 1 Circumstances associated to TT false-negative results 

Technical circumstances Biological circumstances
Poorly conserved tuberculin, exposed to sunlight; contamination by fungi; wrong dilution; maintenance in inadequate vials and denaturation; deep injection or insufficient quantity; use of inadequate needles or syringes; delay administration in relation to preparation time; inexperienced or skewed reader. Severe or disseminate tuberculosis; other acute viral, bacterial or fungal infectious diseases; severe immunodepression (AIDS, use of corticosteroids or other immunosuppressors or chemotherapy); vaccination with live virus; neoplasms, especially of the head-and-neck and lymphoproliferative diseases; malnutrition, diabetes mellitus, renal insufficiency and other metabolic conditions; pregnancy, infants under 3 months of age; elderly (> 65 years old); ultraviolet light; fever during TT and in subsequent hours; benign or malignant lymphogranulomatosis; severe dehydration; sarcoidosis, hypothyroidism (false negative reaction), post chemoprophylaxis with isoniazid and in 5% of cases idiopathic.

The loss of skin test reactivity occurs in cases of malignancy, syphilis, severe systemic viral infection, sarcoidosis, malnutrition and concomitant HIV infection. In all these conditions, cellular immunity is depressed and, thus the absence of skin test reactivity correlates with increased susceptibility to infection by M. tuberculosis. 2 , 6 , 16 , 40

In many individuals, sensitivity to PPD skin test persists throughout life. However, if all mycobacterial organisms and their antigens are eliminated, the number of PPD-specific T cells will decrease with time and in some individuals the response to tuberculin skin test may be negative. If PPD is administered to these individuals, whose skin tests have become attenuated, a stress response may occur in repeated tests. This is called the booster effect and can be misinterpreted as a shift in the skin test result. This is very important nowadays, with the use of biological drugs and the possible repetition of PPD during treatment. Originally negative PPD can become positive without any active infection. The Center for Disease Control (CDC) recommends that when a periodic test is performed, as the annual monitoring on hospital personnel, individuals who responded negatively to the initial skin test must repeat it a week after the original test. If the second test is positive, the booster effect occurred. If it is negative, the subsequent change of PPD skin test result can be accurately interpreted as infection.55 - 58


The cutaneous tuberculosis (TBC) classification covers a wide variety of clinical presentations. Infection can occur through exogenous routes, i.e., cutaneous inoculation takes place directly on the skin (tuberculous chancre, tuberculosis verrucosa cutis and some cases of lupus vulgaris) or endogenous ones, with cutaneous involvement occurring secondarily, through hematogenous route from a distant tuberculosis focus or by contiguity from an already established focus (most cases of lupus vulgaris, scrofuloderma, miliary tuberculosis and orificial tuberculosis).2 , 3 , 5 , 6 , 59 - 61

It is also possible to discriminate according to the bacterial load of the lesions. Cases with many acid-fast bacilli (AFB) seen on direct examination or microscopically are classified as multibacillary otherwise they are called paucibacillary.61 , 62


It is characterized by the appearance at the first site of inoculation, 2 to 4 weeks post contact, of a shallow, painless ulcer, with granular base with microabscesses or thick crust, undermined borders, accompanied by painful regional lymphadenopathy that may evolve with fistulae and, less often, erythema nodosum. Spontaneous regression with scarring and regional lymph node calcification may occur or the patient may develop lupus vulgaris lesions and tuberculosis verrucosa.2 , 5 , 16

It is rare, but more frequent in children who were not vaccinated and have contact with patients with pulmonary tuberculosis.60 , 63 , 64 It has also been reported in surgical wounds, tattoos and piercing sites.61 , 65 There is often dissemination to regional lymph nodes and lymphatic vessels; the combination of the latter with tuberculous chancre is analogous to the Ghon complex in the lungs.2

PPD is initially negative, but becomes positive during the course of the disease (usually after 15 days).16

Histopathology initially shows an acute neutrophilic inflammatory reaction, prolific in AFB and necrotic areas. After 3 to 6 weeks, the lesion acquires a granulomatous appearance with enlarged giant cells and decreased number of bacilli.5 , 61

Among the differential diagnoses are those diseases that may present sporotrichoid patterns: sporotrichosis, leishmaniasis, atypical mycobacteriosis, syphilis, cat scratch disease and tularemia.2 , 60


It appears as painless, isolated or multiple verrucous and tuberous papules, of slow evolution and spontaneous involution, without adenopathy, usually located on the extremities. Its most frequent location is on the hands and it results from exogenous inoculation (Figure 1A). It can be considered an occupational disease, due to self-inoculation possibilities, such as may occur to a dentist treating the mouth of a patient with pulmonary TB or to a butcher handling contaminated meat (in the latter case it is usually due to infection by M. bovis). PPD test is strongly positive.2 , 16 , 60 , 66 , 67

FIGURE 1  A. Tuberculosis verrucosa – verrucous plaque with scaling located on the right axilla; B. Lupus vulgaris (Courtesy from Dr. Marcelo Lyra - Fiocruz); C. Lupus vulgaris (Courtesy from Dr. Marcelo Lyra - Fiocruz); D. Lupus vulgaris – erythematous infiltrating plaque with crusts located on the buttocks 

Histopathology shows pseudoepitheliomatous hyperplasia and hyperkeratosis, tuberculoid granulomas with or without necrosis and rarely with bacilli. Visualization of mycobacteria and/or their isolation in culture are exceptions and not the rule.5 , 60 , 62

As differential diagnosis, diseases with verrucous lesions should be considered, such as: paracoccidioidomycosis, leishmaniasis, sporotrichosis, tuberculosis verrucosa and chromomycosis. Lobomycosis, atypical mycobacteriosis, hypertrophic lichen planus, verrucous carcinoma, iododerma, bromoderma, verruca vulgaris, keratoacanthoma centrifugum and pyoderma vegetans should also be considered.2 , 5 , 6 , 66


It is a form of cutaneous TB that occurs in previously sensitized individuals, with delayed hypersensitivity reaction strongly positive to tuberculin. It may also develop secondarily to TB verrucosa cutis, scrofuloderma or BCG inoculation. Infection occurs endogenously, through a lymphohematogenous route or by continuity, and rarely via exogenous routes.2 , 16

The most characteristic clinical feature is a papulo-tuberous lesion of slow evolution, which can coalesce into a plaque, located on the face, and may invade mucosae. At diascopy, the classic appearance is described as " apple jelly nodules." Lesions may also be flat (serpiginous or polycyclic), hypertrophic (keratotic or tumoral), ulcerated (necrosis and ulceration of the plaque, with cicatricial deformities and mutilations) and vegetative (necrosis and ulceration without scarring). Lesions affecting the earlobe may resemble a pseudotumor. Multiple lesions may appear simultaneously, after a temporary immunosuppression (Figures 1B, 1C and 1D).2 , 5 , 59 , 68 , 69 , 70

FIGURE 2  A. Scrofuloderma (Courtesy from Dr. Vitor Paulo Perez - Fiocruz); B. Chest X-ray in posterioranterior (PA) position showing a right infraclavicular opacity (red arrow), images of thick-walled cavities, acinar lesions permeating the left superior lobe (blue arrow) and pleural effusion on the left (yellow arrow). Pulmonary tuberculosis – Chest X-ray from the same patient on Figure 3 (Courtesy fsrom Dr. Vitor Paulo Perez - Fiocruz); C. Scrofuloderma (Courtesy from Dra. Julia Ocampo Lyra da Silva – Bonsucesso Federal Hospital); D. Scrofuloderma. Ulcerated nodular lesion on the left inguinal region of an HIV positive patient 

The usefulness of dermatoscopy in the diagnosis of lupus vulgaris has been recently suggested, since it revealed peculiar characteristics consisting of linear telangiectasias on a yellow to golden background and whitish reticular streaks. Although none of the observed characteristics are specific enough alone, their combination may increase the diagnostic sensitivity.71

Histopathology will show pseudoepitheliomatous hyperplasia and multiple, well developed tuberculoid granulomas, with scarce caseous necrosis, and nonspecific inflammatory infiltrate without visible bacilli. Mycobacterial culture is often negative. PPD result, however, is usually positive.5 , 16 , 72


It is the most common form in our midst, occurring in children and young people. The infection route is always endogenous, usually secondary to bone or lymph node TB. Clinical lesions appear as nodules, gumma and ulcerations due to fistulae. There are reports of involvement of cervical and inguinocrural regions, as well as lesions in epididymis, conjunctiva and mouth. Patients may have active pulmonary or pleural disease with systemic symptoms (Figure 2).2 , 5 , 73 , 74 , 75

FIGURE 3  A. Papulonecrotic tuberculid – erythematous papules with central crust; B and C: Erythema induratum of Bazin 

Histopathology shows tuberculoid granuloma with wedge-shaped caseous necrosis. AFB are easily seen in biopsy material and / or on exudate direct examination. PPD is strongly positive.5 , 16 , 74 , 75

Differential diagnoses include gummous and fistulous diseases, such as tertiary syphilis, paracoccidioidomycosis, actinomycoses, hidradenitis suppurativa, and lymphogranuloma venereum.6 , 74 , 76


It results from the propagation of tuberculosis infection at the mucocutaneous junction of natural orifices (mouth, anus, vulva, urethra and palate), due to self-inoculation from an active focus on deep tissues, in patients with severe TB on the corresponding area (intestine, urogenital tract). This form of cutaneous tuberculosis is rare and usually affects immunocompromised patients.2 , 77

The most common lesion is a painless ulcer, with fibrinous and pseudomembranous basis. Occasionally, there is no ulcer, however the remnants of a lupus vulgaris hypertrophic tissue or plaque can be observed. Lesions may be localized in any part of the oral and perineal mucosa.77 - 81

Histopathologically, it is characterized by the presence of tuberculoid granulomas with necrosis and ulceration, with abundant AFB. Culture is generally positive, even with a negative tuberculin response (PPD).5 , 16


Considered as a form of systemic miliary tuberculosis, it occurs in immunocompromised patients and anergic children, with negative PPD.5

It is characterized by numerous erithematouspapulovesicular lesions, occasionally ulceronecrotizing, and sometimes with exanthematous rash. When papules heal, they leave residual hypochromic scars. Cutaneous lesions are the result of bacteremia and the primary focus is often located in the lungs.82 , 83 , 84

Histopathologically, it is characterized by the presence of tuberculoid granulomas with necrosis and ulceration, with numerous AFB.5 , 16 , 84


These are acute or chronic skin conditions, punctuated by acute bouts, with a tendency to spontaneous involution of the hyperergic expression following M. tuberculosis infection, active TB or episodic bacteremia. They may occur in the presence of cutaneous tuberculosis or even after BCG vaccination. It is more common amongst children and young adults. Clinical forms usually have a symmetrical distribution, absence of AFB in the lesions (low positivity to PCR), positive PPD and good therapeutic response with favorable outcomes.2 , 3 , 5 , 6 , 16 , 40

Currently only three entities are considered true tuberculids: papulonecrotic form, erythema induratum of Bazin and lichen scrofulosorum (LS).60 , 61 , 62


It appears as painless, symmetrical erythematous or violaceous papulonodular lesions, which evolve in bouts, leaving depressed scars (varioliform or punched-out), located particularly on the extensor surfaces of legs and forearms, dorsal areas of hands and buttocks of children and young adults. PCR positivity and response to specific treatment are observed (Figure 3A).2 , 60 , 62 , 85 , 86

Histopathology reveals marked leukocytoclastic vasculitis in early lesions and tuberculoid granuloma in older lesions, suggesting that it is initially an Arthus phenomenon (type III reaction) and subsequently a delayed hypersensitivity reaction (type IV). Other findings are dermis-based wedge-shaped necrosis, associated with prominent perivascular mononuclear cells infiltration, without AFB.5 , 16

Differential diagnosis should be made with: pityriasis lichenoides et varioliformis acuta (PLEVA), leukocytoclastic necrotizing vasculitis, pruritus and secondary syphilis.2 , 5


This is a rare form in our midst. It is characterized by small, shiny, usually perifollicular erythematous-brownish papules, cover by a crust or by hyperkeratosis; asymptomatic, they appear mostly grouped and in a nummular distribution, located preferably on the trunk, most often in children. Patients show a strong positive reaction to PPD, measuring 18 mm or more. History of BCG vaccination is present in approximately 70% of patients.4 Lichen scrofulosorum was recently described after BCG vaccination and M. avium infection.3 , 5 , 16 , 87 , 88

Histopathology shows superficial granulomas with little or no caseous necrosis in follicles and sudoriparous glands or in their midst. The presence of bacilli is rare, although PCR tests have found M. tuberculosis DNA in these lesions.5 , 16

Differential diagnosis: lichen planus and lichen nitidus, syphilid lichenoides, eczematid, keratosis pilaris, pityriasis rubra pilaris (PRP) and micropapular sarcoidosis.2 , 3 , 5 , 16


At Saint-Louis Hospital in Paris (1861), Bazin described a nodular eruption that occurred on the lower limbs of young women suffering from tuberculosis, under the name of "érythème induré des scrofuleux".89 It is clinically characterized by painless, chronic and recurrent erythematous-violaceous nodules and plaques, with a tendency to ulcerate centrally, which occurs in 30% of cases; lesions are located preferably in women's calves (Figures 3B and 3C).90 , 91 The ulcers are shallow, with violaceous loose borders, granular red basis with yellow dotting.89 , 92 As the lesions evolve, some patients report pain during pressure. Lesions are often symmetric and in the course of evolution, provoke the adhesion of the overlying epidermis thus becoming hardened. The skin has a red-dish-brown or purplish coloration.2 , 3 , 5 , 90 It may be precipitated by cold weather or venous stasis and association with erythrocyanosis and follicular keratosis is often seen.89 , 90 , 91 It may also be associated with varicose veins, livedo, and cold edema. The identical clinical presentation that is not associated with tuberculosis is called nodular vasculitis of Montgomery.2

The skin surface tends to flake when the nodes are well established, forming a collarette around the lesions or crusts covering the ulcers.2 , 91 Some lesions spread forming subcutaneous plaques.89 Most lesions disappear spontaneously within a few months, leaving post-inflammatory hyperpigmentation, and occasionally atrophic pigmented scars.91 , 92

Epidemiological studies allow us to establish solid knowledge: higher predisposition rates for females, adolescents and young adults, predisposition in Caucasians, high incidence in lower temperature countries (colder months) and an apparent association with circulatory disorders of lower limbs and obesity.6 , 16 , 91 The disease has a chronic course and ulcerations and new lesions may appear during treatment.90 , 91

Clinically, erythema induratum of Bazin can mimic a variety of conditions that present as chronic nodules on the lower extremities, including erythema nodosum, cutaneous polyarteritis, pancreatic panniculitis, lupus profundus, subcutaneous sarcoidosis and cutaneous T-cell lymphoma.91

Histopathology consists of tuberculoid granulomatous infiltrate, vascular alterations and areas of caseous necrosis. The process is primarily located in the hypodermis, the center stage for reactions in which venules and small to medium caliber arteries are affected.5 , 6 Vascular walls may show several changes: thickening, edema, hyalinization, necrosis and invasion by cell infiltrate. The altered vascular endothelium may present a simple swelling or partial / complete proliferation with obliteration of the lumen leading to thrombosis and necrosis.15 , 16 Cellular infiltrate is form by lymphocytes, histiocytes, epithelioid and giant cells. It is interposed between adipose cells that are progressively replaced - proliferative atrophy ("wucheratrophie").15 , 91 , 93 - 96

It is the opinion of the authors that, when qualified laboratory techniques are not available for the molecular diagnosis of a likely tuberculosis infection and proof of the infectious agent, one should proceed with a therapeutic test and observation of outcome. We highlight that in these cases the patient should be informed of the decision and of the possibility that the lesions will not resolve, however, according to the authors' experience, most cases respond to treatment.


Latent tuberculosis infection (LTBI), defined as positive PPD, negative bacteriological analysis and lack of clinical or radiological evidence of active tuberculosis, should be considered in patients treated with immunobiological therapies because of the high risk of developing active TB. Performing the diagnostic tests capable of excluding LTBI is an essential step before initiating treatment. All biologic drugs, especially anti-TNF-α antibodies, can lead to reactivation of M. tuberculosis infection, and a detailed patient history of previous disease or contact with tuberculosis is mandatory, in addition to thoracic radiography (x-ray) and PPD.97 , 98

In asymptomatic patients, tuberculin skin test is initially recommended and, if the induration is equal to or larger than 5 mm (PPD reactor), chest X-rays should be performed. If chest X-rays are normal, chemoprophylaxis is recommended (treatment of latent TB) with isoniazid at 5 to 10 mg/kg to a maximum dose of 300 mg/day. It must be maintained for a minimum of six months. There is evidence, however, that continuing treatment for nine months offers more protection than keeping it for only six months, especially in patients with HIV/AIDS.1 , 99 - 103 Operational feasibility and patient compliance should be considered when choosing between six and nine months of treatment. If chest X-rays are altered (suspect image or tuberculosis sequelae), specific treatment should be implemented. The recommendation is that biological therapy should begin after 1-2 months of starting prophylaxis or after the clinical treatment of active disease, following clinical evaluation.97 , 98


Currently the diagnosis of tuberculosis may already include detection, identification of species / complex and determination of the etiologic agent's drug sensitivity. Besides a suggestive clinical presentation, probability criteria include: histopathology with tuberculoid granuloma with caseous necrosis; granuloma without necrosis, but with positive tuberculin skin test or TB confirmed in another organ and a successful therapeutic test after a week. Culture and species identification (Lowenstein, Bactec, PCR) are used to confirm the diagnosis.5 , 6

Culture is a method of high specificity and sensitivity in diagnosing TB. Classical methods of mycobacteria culture use sample seeding in solid media: Lowenstein-Jensen and Ogawa-Kudoh. The time to detect bacterial growth ranges from 14 to 30 days and may extend up to eight weeks. Streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide are the antimycobacterial drugs usually tested.15 , 16

Species identification is made by biochemical and phenotypic methods or using molecular techniques analyses. Culture for mycobacteria is indicated if there is a suspicion of cutaneous tuberculosis and atypical mycobacteriosis.1 , 5

Culture with identification and susceptibility testing are indicated in the following cases: patients with history of previous treatments, regardless of the time elapsed; immunocompromised patients, especially patients with HIV; anti-TB treatment failure; investigation of populations at higher risk of harboring resistant strains of M. tuberculosis (health care professionals, homeless, prisoners, patients admitted to long-term facilities or hospitals that do not adopt biosecurity measures) or which are difficult to approach for follow-up (indigenous).1 , 5 , 6 , 15 , 16

The authors suggest an algorithm for the management of patients with lesions that are suspected to be cutaneous tuberculosis (Figure 4).

FIGURE 4 Algorithm for the management of cutaneous tuberculosis: 


These are immunological tests based on cellular response stimulation through peptides that are absent from BCG and most non-tuberculous mycobacteria. They assess sensitization to M. tuberculosis by measuring the amount of INF gamma released by lymphocytes confronted with M. tuberculosis-specific antigens, such as ESAT-6 (early secretory antigenic target-6) and CFP-10 (culture filtrate protein 10). ESAT-6 and CFP-10 are present in M. kansasii, M. marinum and M. szulgai, and sensitization to such organisms may contribute to the release of IFN-γ in response to these antigens, leading to false-positive results.1 , 104

Two tests approved by the FDA (Food and Drug Administration) are QuantiFERON-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB. These tests are still not recommended for use in routine diagnosis of active and / or latent TB in our midst.104


Molecular tests for TB diagnosis are based on the amplification and detection of specific nucleic acid sequences of M. tuberculosis complex in clinical specimens; known as nucleic acid amplification test (NAAT), they provide results in 24 to 48 hours. Importantly, NAAT was approved in industrialized countries only for use in respiratory samples, i.e., for the investigation of pulmonary TB in adult patients without previous history of anti-TB treatment. It should not be used to monitor treatment, nor replace culture tests for mycobacteria.1 , 105

Tests of mycobacterial sensitivity to antituberculosis drugs can be used to define the therapeutic regimen for an individual or to plan strategies for large-scale treatments. Resistance can be defined as an in vitro decrease of M. tuberculosis' susceptibility, for each drug, compared with the wild type strain (which never had contact with the drug). Tests may be classified in 2 types: phenotypic and genotypic.106 , 107 The main characteristics of each method are presented in chart 2.1 , 106 , 108 - 113

CHART 2 Mycobacterial sensitivity phenotypic and genotypic tests 

Phenotypic Methods  
Proportional Method106 It consists in detecting the proportion of resistant strains present in a sample of M. tuberculosis tested with a drug concentration that is able to inhibit the growth of susceptible cells, but not of resistant cells. It is a sensible and cost-effective methodology, however, the results are only available after 60 days
BACTEC 460106 , 108 The device detects radioactive CO2 released from the use of C14 palmitic acid, present in the liquid culture medium based on Agar, consumed by mycobacteria. It is a sensitive methodology and provides results within 14 days, however it is costly, and uses radioactive material, which is difficult to discard. It has 95 to 97% agreement rate with the proportional method
BACTEC-MGIT 9601 , 106 , 109 , 110 The device does not use radioactive material because the agar-based culture medium is composed of fluorescent material. Microorganism growth is visualized by spectropho-tometry. It has similar performance to that of proportional method with an average detection time of seven days. In Brazil, it is considered the gold standard. It is validated and approved by ANVISA for the following drugs: streptomycin, isoniazid, rifampicin and ethambutol.
MODS (Microscopic Observation Broth Drug Susceptibility Assay)1 , 106 , 111 The MODS technique permits, after eight days, the visualization of the cord factor, formed by growing mycobacteria and seen in an inverted light with darkfield filter microscopy. Because of the trehalose dimycolate glycolipid present in the bacterial cell walls, the growth of M. tuberculosis complex in microscopic serpentine cords, called cord factor or cord growth, in which acid-fast bacilli (AFB) are arranged in parallel chains, can be seen in appropriate conditions in virulent strains of TB bacillus. It has sensitivity and specificity similar to those of traditional methods of culture.
D29-PhaB Assay106 It is based on the ability of the mycobacteriophage of infecting the cells when the myco-bacterium is drug-resistant. When the phage infects the cells, it can lyse the cell wall thus detecting resistance.
E-Test1 , 106 , 112 It is a quantitative sensitivity test, and results can be obtained from five to ten days following the growth of M. tuberculosis in culture medium. It has high concordance rates, for the detection of multidrug-resistant strains, when compared with the proportional method. Because it is inexpensive, it can be an option for the rapid diagnosis of myco-bacterial resistance in developing countries.
Genotypic Methods  
Sequencing106 It analyzes all nucleotide from a specific DNA region chosen on the genome. It allows the identification of mutations in the resistant strain, which may be related to resistance to certain drugs. It is considered the gold standard when it comes to diagnosis by molecular biology techniques.
PCR-SSCP (Single Strand Conformation Polymorphism)1 , 106 , 113 It uses the analysis of the amplification product obtained from the DNA target region in the mycobacterial genome. It permits the identification of alterations in amplified geno-mic regions. It is a fast method (24 hours).


Tuberculosis is curable in virtually 100% of new cases that are sensitive to anti-TB drugs, as long as the basic principles of drug therapy and the proper treatment operationalization are observed.1 , 5

In 1979, Brazil proposed a TB treatment system comprised of 2RHZ/4RH for new cases of pulmonary and extrapulmonary TB, except the meningeal form.114 This scheme consists of 2 months of rifampin ®, isoniazid (H) and pyrazinamide (Z) and another four months of only rifampicin and isoniazid. In 2009, ethambutol (E) was added as a fourth drug in the intensive phase of basic scheme treatment (first two months).1 The pharmacological presentation of this scheme became a fixed-dose tablet with a combination of four drugs (RHZE), in the following dosages: R150mg, M 75mg, Z 400mg and E 275mg (Table 1). This medication should be taken once daily.1 , 5

TABLE 1 2RHZE/4RH scheme for newly diagnosed cases in adults and adolescents (> 10 years old), for all forms of cutaneous diagnosis, infected by HIV or not 

Scheme Drugs Weight range Unit/dose Months
2 RHZE RHZE 20kg to 35kg 2 tablets 2
Intensive phase 150/75/400/275 Fixed-dose combined drug tablet 36kg to 50kg 3 tablets  
> 50kg 4 tablets  
4 RH RH 20kg to 35kg 1 tablet or capsule 300/200mg or 2 tablets 150/75 4
Maintenance phase 300/200 or 150/100 tablets or capsules or 150/75 tablets 36kg to 50kg 1 tablet or capsule 300/200mg + 1 tablet or capsule 150/100mg or 3 tablets 150/75  
    > 50kg 2 tablets or capsules 300/200mg or 4 tablets 150/75  

For children (under 10 years old) the recommendation of RHZ persists (Table 2). In children under 5 years old with difficulty to ingest tablets, the use of drugs in syrup or suspension forms is recommended. Medications should be administered preferably during fast (one hour before or two hours after breakfast), in one take, or in case of digestive intolerance, with a meal. Cutaneous TB treatment should last six months, as well as the treatment of patients coinfected with HIV, regardless of the stage of evolution of viral infection.1

TABLE 2 2RHZ/4RH scheme for newly diagnosed cases in children (< 10 years old), for all forms of cutaneous diagnosis, infected by HIV or not 

Treatment phases Drugs Weight range      
    Up to 20kg mg/kg/day >21kg to 35kg mg/day >36kg to 45kg mg/day > 45kg mg/day
2 RHZ R 10 300 450 600
Attack phase H 10 200 300 400
  Z 35 1000 1500 2000
4 RH R 10 300 450 600
Maintenance H 10 200 300 400

Source - Guide: recommendations for tuberculosis control in Brazil, 2011.

If retreatment is necessary, 2RHZE/4RH regimen should be initiated until culture results and susceptibility testing are back. Cases progressing to treatment failure should be carefully evaluated for therapeutic history, adherence to previous treatments and evidence of drug resistance.1

The recommended treatment for erythema induratum of Bazin is similar to that for new cases of pulmonary and extrapulmonary TB, with rifampicin, isoniazid, pyrazinamide and ethambutol taken for two months, only rifampicin and isoniazid taken for another four months.1 The difference however, is that treatment with isoniazid 400 mg / day must be maintained for a longer period of time, up to two years.6 , 15 , 91 Pyridoxine should be added to the treatment to prevent peripheral neuropathy.1 Tuberculin protein in various dilutions is used for desensitization as an adjuvant, as well as corticosteroids. Potassium iodide, dapsone, gold salts and doxycycline are cited as adjuvant treatments and some studies have reported satisfactory results.91 , 92

Special attention should be given to the treatment of groups considered at high risk for toxicity, consisting of people over 60, in poor health conditions, alcoholics, HIV-infected, those in concomitant use of anticonvulsants and with hepatic disorders.1

The RHZE scheme can be administered in usual doses for pregnant women and the use of pyridoxine (50mg/day) during pregnancy is recommended because of the risk of neurological toxicity (due to isoniazid) to the newborn. There are no contraindications to breastfeeding, as long as the mother does not have tuberculous mastitis, however special attention on monitoring of adverse effects is necessary.1

Patients with hepatic diseases should be monitored with serial assessment of liver enzymes (Table 3). In nephropathic patients it is necessary to measure the creatinine clearance levels (before starting the treatment regimen so that dose adjustment may be performed) (Tables 4 and 5).

TABLE 3 Conduct for patients with hepatopathy 

With previous hepatic disease With cirrhosis AST/ALT > 3 x upperlimit of normality (ULN) 2 SRE / 7RE
2 SHE / 10 HE
3 SEO / 9 EO
- Acute viral hepatitis      
    AST/ALT < 3 x ULN Basic scheme
- Chronic hepatopathy: viral, autoimmune and cryptogenic      
- Alcoholic hepatopathy: Hepatic steatosis, alcoholic hepatitis Without cirrhosis 3 SEO / 9 EO  
Without previous hepatic disease AST/ALT 5 x ULN Re-introduction Re-introduction of Basic Scheme or similar
(Hepatotoxicity after the start of treatment) (or 3 x ULN with symptoms) Jaundice RE ➤ H ➤ Z  
  Persistency of AST/ALT 5 x ULN for 4 weeks or severe cases of TB 3 SEO / 9 EO

Source - Guide: recommendations for tuberculosis control in Brazil, 2011.

TABLE 4 Creatinine clearance calculation 

Creatinine Clearance for men (140 - age) x weight (in kg)
72 x creatinine (in mg%)
Creatinine Clearance for women (140 - age) x weight (in kg) x 0.85
72 x creatinine (in mg%)

Source - Guide: recommendations for tuberculosis control in Brazil, 2011.

TABLE 5 Dose adjustment for patients with nephropathy 

Drug Method Creatinine clearance  
    > 50 - 90 10 - 50 < 10
Rifampicin None 100% 100% 100%
Isoniazid Dosage 100% 75 - 100% 50%
Pyrazinamide Time 24h 24h 48 - 72h
Ethambutol Dosage 100% 50-100% 25 - 50%
Streptomycin Time 24h 24-72h 72 - 96h

The association of pyrazinamide to ketoconazole increases the risk of hepatotoxicity. Regarding ethambutol, antacids decrease absorption and dideoxyinosine - DDI - and dideoxycytidine - DDC potentiate peripheral neuritis.1 , 115 , 116 , 117


Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de recomendações para o controle da tuberculose no Brasil. (Ministry of Health. Secretary of Health Surveillance. Department of Epidemiological Surveillance. Guide: recommendations for tuberculosis control in Brazil) Brasília: Ministério da Saúde; 2011. 284 p. [ Links ]

Azulay RD, Azulay DR. Tuberculose cutânea (Cutaneous tuberculosis). In: Azulay DR. Dermatologia. 5. ed. Rio de Janeiro: Guanabara Koogan, 2011:366-73. [ Links ]

Sampaio SAP, Rivitti EA. Tuberculose e micobactérias atípicas (Tuberculosis and atypical mycobacteria). In: Sampaio SAP, Rivitti EA. Dermatologia. 3. ed. São Paulo: Artes Médicas, 2008. p.609-23. [ Links ]

Ministério da Saúde. Secretaria de Vigilância em Saúde. Manual nacional de vigilância laboratorial da tuberculose e outras microbactérias. (Ministry of Health. Secretary of Health Surveillance. National Guide for laboratorial surveillance of tuberculosis and other microbacteria). Brasília, DF, 2008. [ Links ]

Ramos-E-Silva M, Castro MCR. Tuberculose cutânea (Cutaneous tuberculosis). In: Fundamentos de Dermatologia. Rio de Janeiro: Atheneu, 2010:933-42. [ Links ]

Yates VM. Mycobacterial Infections. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th Wiley Blackwell; 2010. p. 31.1-30. [ Links ]

Huiras E, Preda V, Maurer T, Whitfeld M. Cutaneous manifestations of immune reconstitution inflammatory syndrome. Curr Opin HIV AIDS. 2008;3:453-60. [ Links ]

Robertson J, Meier M, Wall J, Ying J, Fichtenbaum CJ. Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy. Clin Infect Dis. 2006;42:1639-46. [ Links ]

Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:251-61. [ Links ]

Hernandez C, Cetner AS, Jordan JE, Puangsuvan SN, Robinson JK. Tuberculosis in the age of biologic therapy. J Am Acad Dermatol. 2008;59:363-80. [ Links ] [Internet]. World Health Organization (WHO). Global tuberculosis report 2012. Country profiles. [cited 2013 maio 08]. Available form: [ Links ]

Sant'Anna CC, Orfaliais CT, March Mde F, Conde MB. Evaluation of a proposed diagnostic scoring system for pulmonary tuberculosis in Brazilian children. Int J Tuberc Lung Dis. 2006;10:463-5. [ Links ] [Internet]. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Programa Nacional de Controle da Tuberculose: dados e indicadores da Tuberculose: números de casos novos. (Ministry of Health. Secretary of Health Surveillance. Department of Epidemiological Surveillance. National Program for Tuberculosis Control: data and indicators of Tuberculosis: number of new cases). Brasília: Ministério da Saúde; 2012. [acesso 04 Fev. 2013]. Disponível em: [ Links ]

Kakakhel KU, Fritsch P. Cutaneous tuberculosis. Int J Dermatol. 1989;28:355-62. [ Links ]

Tappeiner G. Tuberculosis and infections with atypical Mycobacteria. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors. Dermatology in general medicine. 7th ed. New York: McGraw-Hill; 2008. p. 1768-78. [ Links ]

Ramos-E-Silva M, Castro MCR. Cutaneous tuberculosis. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 2th. New York: Mosby Elsevier; 2008. p. 1114-19. [ Links ]

Rocha A, Elias AR, Sobral LF, Soares DF, Santos AC, Marsico AG, et al. Genotyping did not evidence any contribution of Mycobacterium bovis to human tuberculosis in Brazil. Tuberculosis (Edinb). 2011;91:14-21. [ Links ]

Ara M, Seral C, Baselga C, Navarro M, del Pilar Grasa M, Carapeto FJ. Primary tuberculous chancre caused by Mycobacterium bovis after goring with a bull's horn. J Am Acad Dermatol. 2000;43:535-7. [ Links ]

Jaka-Moreno A, López-Núñez M, López-Pestaña A, Tuneu-Valls A. Lupus vulgaris caused by Mycobacterium bovis. Actas Dermosifiliogr. 2012;103:251-3. [ Links ]

Rowland R, McShane H. Tuberculosis vaccines in clinical trials. Expert Rev Vaccines. 2011;10:645-58. [ Links ]

Bricks LF. Percutaneous or intradermal BCG vaccine? J Pediatr (Rio J). 2004;80:93-8. [ Links ] [Internet]. Sociedade Brasileira de Pediatria. Departamento de Infectologia. Berezin EN, Migowiski E, Safadi MAP, et al. Calendário Vacinal Manual 2011/2012. (Brazilian Society of Pediatrics. Department of Infectious Diseases. Vaccine Schedule. 2011/2012 Manual) [acesso 04 Fev. 2013]. Disponível em: [ Links ]

Najem NM, Zadeh VB, Al-Abdulrazzaq AH, Al-Otaibi SR, Kadyan S, Joneja M. Bacillus Calmette-Guérin vaccine- induced lupus vulgaris in a child. Acta Dermatovenerol Alp Panonica Adriat. 2009;18:195-7. [ Links ]

McShane H. Tuberculosis vaccines: beyond bacille Calmette-Guerin. Philos Trans R Soc Lond B Biol Sci. 2011;366:2782-9. [ Links ]

Sehgal VN, Wagh SA. Cutaneous tuberculosis. Current concepts. Int J Dermatol. 1990;29:237-52. [ Links ]

Sehgal VN, Srivastava G, Khurana VK, Sharma VK, Bhalla P, Beohar PC. An appraisal of epidemiologic, clinical, bacteriologic, histopathologic, and immunologic parameters in cutaneous tuberculosis. Int J Dermatol. 198726:521-6. [ Links ]

Teixeira HC, Abramo C, Munk ME. Immunological diagnosis of tuberculosis: problems and strategies for success. J Bras Pneumol. 2007;33:323-34. [ Links ]

North RJ, Jung YJ. Immunity to Tuberculosis. Annu Rev Immunol. 2004;22:599-623. [ Links ]

Winau F, Weber S, Sad S, de Diego J, Hoops SL, Breiden B, et al. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity. 2006;24:105-17. [ Links ]

Kaufmann SH, Schaible UE. Antigen presentation and recognition in bacterial infections. Curr Opin Immunol. 2005;17:79-87. [ Links ]

Teixeira HC, Munk ME, Kaufmann SH. Frequencies of IFN gamma- and IL-4-producing cells during Mycobacterium bovis (BCG) infection in two genetically susceptible mouse strains: role of alpha/beta T cells and NK1.1 cells. Immunol Lett. 1995;46:15-9. [ Links ]

Krutzik SR, Modlin RL. The role of Toll-like receptors in combating mycobacteria. Semin Immunol. 2004;16:35-41. [ Links ]

Ottenhoff TH, Verreck FA, Hoeve MA, van de Vosse E. Control of human host immunity to mycobacteria. Tuberculosis (Edinb). 2005;85:53-64. [ Links ]

Salgame P. Host innate and th1 responses and the bacterial factors that control Mycobacterium tuberculosis infection. Curr Opin Immunol. 2005;17:374-80. [ Links ]

Lin Y, Zhang M, Hofman FM, Gong J, Barnes PF. Absence of a prominent Th2 cytokine response in human tuberculosis. Infect Immun. 1996;64:1351-6. [ Links ]

Swaminathan S, Gong J, Zhang M, Samten B, Hanna LE, Narayanan PR, et al. Cytokine production in children with tuberculous infection and disease. Clin Infect Dis. 1999;28:1290-3. [ Links ]

Conde MB, Melo FA, Marques AM, Cardoso NC, Pinheiro VG, Dalcin Pde T, et al. III Brazilian Thoracic Association Guidelines on Tuberculosis. J Bras Pneumol. 2009;35:1018-48. [ Links ]

Rieder HL, Chadha VK, Nagelkerke NJ, van Leth F, van der Werf MJ; KNCV Tuberculosis Foundation. Guidelines for conducting tuberculin skin test surveys in high-prevalence countries. Int J Tuberc Lung Dis. 2011;15:S1-25. [ Links ]

Arnadottir T, Rieder HL, Trébucq A, Waaler HT. Guidelines for conducting tuberculin skin test surveys in high prevalence countries. Tuber Lung Dis. 1996;77:1-19. [ Links ]

Melo FAF, Savioli MTG, Katz MH, Duarte H, Almeida EA. Tuberculose (Tuberculosis). In: Lopes AC. Tratado de Clínica Médica (Treaty of General Medicine). São Paulo: Roca, 2006:2623-61 [ Links ]

Howard TP, Solomon DA. Reading the tuberculin skin test. Who, when, and how? Arch Intern Med. 1988;148:2457-9. [ Links ]

Beck JS, Gibbs JH, Potts RC, Kardjito T, Grange JM, Jawad ES, et al. Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis. J Pathol. 1989;159:317-22. [ Links ]

World Health Organization. Tuberculosis Research Office. Tuberculin reaction size on 5 consecutive days. Bull World Health Organ. 1955;12:189-196. [ Links ]

Arias Guillén M. Advances in the diagnosis of tuberculosis infection. Arch Bronconeumol. 2011;47:521-30. [ Links ]

MacGregor RR. Cutaneous tuberculosis. Clin Dermatol. 1995;13:245-55. [ Links ]

Sokal JE. Editorial: Measurement of delayed skin-test responses. N Engl J Med. 1975;293:501-2. [ Links ]

Cruz Anleu ID, Velásquez Serratos JR. Childhood tuberculosis. How to diagnose it? Arch Argent Pediatr. 2012;110:144-51. [ Links ]

Shingadia D. The diagnosis of tuberculosis. Pediatr Infect Dis J. 2012;31:302-5. [ Links ]

Khan K, Wang J, Marras TK. Nontuberculous mycobacterial sensitization in the United States: national trends over three decades. Am J Respir Crit Care Med. 2007;176:306-13. [ Links ]

Hansen KN, Heltberg I, Hjelt K. Sensitivity to tuberculin and sensitins from atypical mycobacteria (M. chelonae subsp. abscessus, M. avium, M. intracellulare, M. scrofulaceum) in 100 Danish school children. Dan Med Bull. 1989;36:399-401. [ Links ]

Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med. 1999;159:15-21. [ Links ]

Menzies D, Gardiner G, Farhat M, Greenaway C, Pai M. Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results. Int J Tuberc Lung Dis. 2008;12:498-505. [ Links ]

Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149:177-84. [ Links ]

Ruffino-Netto A. Interpretação da prova tuberculínica (Interpretation of the tuberculin test). Rev Saude Publica. 2006;40:546-7. [ Links ]

Igari H, Watanabe A, Sato T. Booster phenomenon of QuantiFERON-TB Gold after prior intradermal PPD injection. Int J Tuberc Lung Dis. 2007;11:788-91. [ Links ]

Sagheb MM, Goodarzi M, Roozbeh J. The booster phenomenon of tuberculin skin testing in patients receiving hemodialysis. Iran J Immunol. 2008;5:212-6. [ Links ]

Salles CG, Ruffino-Netto A, Lapa-e-Silva JR, Kritski AL, Cailleaux-Cesar M, Queiroz-Mello FC, et al. The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort. BMC Public Health. 2007;7:38. [ Links ] [Internet]. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Division of Tuberculosis Elimination. Latent tuberculosis infection: a Guide for Primary Health Care Providers. Medical School Global Tuberculosis Institute 2010. [cited 2013 Feb 4]. Disponível em: [ Links ]

Fariña MC, Gegundez MI, Piqué E, Esteban J, Martín L, Requena L, et al. Cutaneous tuberculosis: a clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol. 1995;33:433-40. [ Links ]

Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 2007;25:173-80. [ Links ]

Concha RM, Fich S F, Rabagliati B R, Pinto S C, Rubio L R, Navea D O, et al. Cutaneous tuberculosis: two case reports and review. Rev Chilena Infectol. 2011;28:262-8. [ Links ]

Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a practical case report and review for the dermatologist. J Clin Aesthet Dermatol. 2009;2:19-27. [ Links ]

Liang MG, Rooney JA, Rhodes KH, Calobrisi SD. Cutaneous inoculation tuberculosis in a child. J Am Acad Dermatol. 1999;41:860-2. [ Links ]

Manicatide E, Claiciu I. Tuberculosis in children caused by primary inoculation of the skin and mucous membranes. Pediatria (Bucur). 1974;23:49-58. [ Links ]

Kluger N. Cutaneous infections related to permanent tattooing. Med Mal Infect. 2011;41:115-22. [ Links ]

Rajan J, Mathai AT, Prasad PV, Kaviarasan PK. Multifocal tuberculosis verrucosa cutis. Indian J Dermatol. 2011;56:332-4. [ Links ]

Kakakhel K. Simultaneous occurrence of tuberculous gumma, tuberculosis verrucosa cutis, and lichen scrofulosorum. Int J Dermatol. 1998;37:867-9. [ Links ]

Varas MC, Nieme SC, Barría MC. Cutaneous tuberculosis. Report of one case. Rev Med Chil. 2012;140:493-8. [ Links ]

Sacchidanand S, Sharavana S, Mallikarjun M, Nataraja HV. Giant lupus vulgaris: A rare presentation. Indian Dermatol Online J. 2012;3:34-6. [ Links ]

Kohli PS, Kumar V, Nibhoria S. Tuberculous otitis media and lupus vulgaris of face: an unusual association. Indian J Otolaryngol Head Neck Surg. 2011;63:71-4. [ Links ]

Micali G, Lacarrubba F, Massimino D, Schwartz RA. Dermatoscopy: alternative uses in daily clinical practice. J Am Acad Dermatol. 2011;64:1135-46. [ Links ]

Fenniche S, Ben Jennet S, Marrak H, Khayat O, Zghal M, Ben Ayed M, et al. Cutaneous tuberculosis: anatomoclinical features and clinical course (26 cases). Ann Dermatol Venereol. 2003;130:1021-4. [ Links ]

Ramos-E-Silva M, Marques AS, Rocha GL. Tuberculose cutânea associada à tuberculose osteoarticular (Cutaneous tuberculosis associated with osteoarticular tuberculosis). An Bras Dermatol. 1986;61:245-50. [ Links ]

Martins Junior EV, Marques BP, Reis Neto ET, Lima BCMLS, Neumann YRB. Disseminated cutaneous tuberculosis with scrofuloderma associated to costal arch tuberculosis. An Bras Dermatol. 2007;82:343-7. [ Links ]

Angel DI, Alfonso R, Faizal M, Ricaurte O, Baez JA, Rojas A, et al. Cutaneous tuberculosis diagnosis in an inhospitable Amazonian region by means of telemedicine and molecular biology. J Am Acad Dermatol. 2005;52:S65-8. [ Links ]

Sehgal VN, Jain MK, Srivastava G. Changing pattern of cutaneous tuberculosis. A prospective study. Int J Dermatol. 1989;28:231-6. [ Links ]

Zielonogora J, Assis TL, Azulay RD. Tuberculose cutânea: aspectos clínicos, etiopatogenia e dados epidemiológicos (Cutaneous tuberculosis: clinical aspects, etiopathogenesis and epidemiological data). An Bras Dermatol. 1989;64:211-6. [ Links ]

Jiménez-Gallo D, Navas-García N, Albarrán-Planelles C, Guerrero-Sánchez F. Periorificial cutaneous tuberculosis of the vulva. Actas Dermosifiliogr. 2012;103:929-30. [ Links ]

Ferreira OC1, Osório F, Lisboa C, Silva MJ, Eloy C, Paiva ME, Azevedo F. et al. Scrotal ulcers revealing pulmonary and genitourinary tuberculosis. Dermatol Online J. 2011;17:10. [ Links ]

Dlova NC. Tuberculosis cutis orificialis. Skinmed. 2006;5:53. [ Links ]

Sehgal VN, Chaudhry AK, Gupta R. Autoinoculation lupus vulgaris of the perineum. Genitourin Med. 1991;67:348-9. [ Links ]

Ko JH, Shih YC, Huang YH, Lu CF, Yang CH. Acute tuberculosis cutis miliaris disseminata in a patient with systemic lupus erythematosus. Int J Dermatol. 2011;50:1279-82. [ Links ]

del Giudice P, Bernard E, Perrin C, Bernardin G, Fouché R, Boissy C, et al. Unusual cutaneous manifestations of miliary tuberculosis. Clin Infect Dis. 2000;30:201-4. [ Links ]

High WA, Evans CC, Hoang MP. Cutaneous miliary tuberculosis in two patients with HIV infection. J Am Acad Dermatol. 2004;50:S110-3. [ Links ]

Jun R, Xiao-Kun L, Chao P, Xin-Sheng L, Xiao-Hui W, Xin Y, et al. Papulonecrotic Tuberculid with Positive Acid-fast Bacilli. Indian J Dermatol. 2013;58:85. [ Links ]

Niemeyer-Corbellini JP, Spinatto D, Boechat N, Carvalho AC, Pineiro-Maceira J, Azulay DR. Papulonecrotic tuberculid on the scalp. Int J Dermatol. 2008;47:1028-32. [ Links ]

Camacho D, Pielasinski U, Revelles JM, Górgolas M, Manzarbeitia F, Kutzner H, et al. Lichen scrofulosorum mimicking lichen planus. Am J Dermatopathol. 2011;33:186-91. [ Links ]

Singhal P, Patel PH, Marfatia YS. Lichen scrofulosorum: A diagnosis overlooked. Indian Dermatol Online J. 2012;3:190-2. [ Links ]

Nascimento LV. Tuberculose Cutânea Indurativa (Erythema induratum of Bazin). [tese]. Rio de Janeiro (RJ): Universidade Federal do Rio de Janeiro; 1982. [ Links ]

Nascimento LV. Mycobacteria: Tuberculosis. In Tyring SK, Lupi O, Hengge UR. Tropical Dermatology. Philadelphia: Elsevier Churchil Livingstone; 2006, p 251. [ Links ]

Sharon V, Goodarzi H, Chambers CJ, Fung MA, Armstrong AW. Erythema induratum of Bazin. Dermatol Online J. 2010;16:1. [ Links ]

Mascaró JM Jr, Baselga E. Erythema induratum of Bazin. Dermatol Clin. 2008;26:439-45, v. [ Links ]

Segura S, Pujol RM, Trindade F, Requena L. Vasculitis in erythema induratum of Bazin: a histopathologic study of 101 biopsy specimens from 86 patients. J Am Acad Dermatol. 2008;59:839-51. [ Links ]

Yen A, Fearneyhough P, Rady P, Tyring S, Diven D. Erythema induratum of Bazin as a tuberculid: confirmation of Mycobacterium tuberculosis DNA polymerase chain reaction analysis. J Am Acad Dermatol. 1997;36:99-101. [ Links ]

Angus J, Roberts C, Kulkarni K, Leach I, Murphy R. Usefulness of the QuantiFERON test in the confirmation of latent tuberculosis in association with erythema induratum. Br J Dermatol. 2007;157:1293-4. [ Links ]

Nascimento LV. Tuberculose Cutânea (Cutaneous tuberculosis). In: Costa A, Alves G, Azulay L. Dermatologia e Gravidez (Dermatology and Pregnancy). Rio de Janeiro: Elsevier; 2009. p. 253. [ Links ]

Sociedade Brasileira de Dermatologia. Consenso Brasileiro de Psoríase 2009. (Brazilian Society of Dermatology. Brazilian Consensus on Psoriasis 2009). Rio de Janeiro: SBD; 2009. 115p. [ Links ]

Lima EA, Lima MA. Avaliação pré-tratamento biológico. (Assesment before treatment with biological drugs). In: Romiti R. Compêndio de psoríase. Rio de Janeiro: Elsevier; 2010. p. 186-97. [ Links ]

Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis. 1999;3:847-50. [ Links ]

Moulding T. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis. 2000;4:485-6. [ Links ]

American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Journal of Respiratory and Critical Care Medicine, MMWR Recomm Rep. 2000;49(RR-6):1-51. [ Links ]

Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med. 2000;161:S221-47. [ Links ]

Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ. 1982;60:555-64. [ Links ]

Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K; et al. Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection. United States. MMWR Recomm Rep. 2010;59:1-25. [ Links ]

Trajman A, Pai M, Dheda K, van Zyl Smit R, Zwerling AA, Joshi R, et al. Novel tests for diagnosing tuberculous pleural effusion: what works and what does not? Eur Respir J. 2008;31:1098-106. [ Links ]

Rodrigues VFS. Caracterização de mutações associadas com a resistência à pirazinamida e etambutol em isolados de Mycobacterium tuberculosis. (Characterization of mutations associated with pyrazinamide and ethambutol resistance in Mycobacterium tuberculosis isolates). [Tese]. Porto Alegre (RS): Universidade Federal do Rio Grande do Sul; 2005. 121 p. [ Links ]

Migliori GB, Matteelli A, Cirillo D, Pai M. Diagnosis of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis: Current standards and challenges. Can J Infect Dis Med Microbiol. 2008;19:169-72. [ Links ]

Garrigó M, Aragón LM, Alcaide F, Borrell S, Cardeñosa E, Galán JJ, et al. Multicenter laboratory evaluation of the MB/BacT Mycobacterium detection system and the BACTEC MGIT 960 system in comparison with the BACTEC 460TB system for susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2007;45:1766-70. [ Links ]

Rudeeaneksin J, Bunchoo S, Srisungngam S, Sawanpanyalert P, Chamnangrom S, Kamolwat A, et al. Rapid identification of Mycobacterium tuberculosis in BACTEC MGIT960 cultures by in-house loop-medicated isothermal amplification. Jpn J Infect Dis. 2012;65:306-11. [ Links ]

Fonseca Lde S, Vieira GB, Sobral LF, Ribeiro EO, Marsico AG. Comparative evaluation under routine conditions of the nitrate reduction assay, the proportion assay and the MGIT 960 assay for drug susceptibility testing of clinical isolates of Mycobacterium tuberculosis. Mem Inst Oswaldo Cruz. 2012;107:142-4. [ Links ]

Coelho AG, Zamarioli LA, Reis CM, Duca BF. Detection of cord factor for the presumptive identification of Mycobacterium tuberculosis complex. J Bras Pneumol. 2007;33:707-11. [ Links ]

Coban AY, Bilgin K, Uzun M, Akgunes A, Yusof A, Durupinar B. Comparative Study for Determination of Mycobacterium tuberculosis Susceptibility to First- and Second-Line Antituberculosis Drugs by the Etest Using 7H11, Blood, and Chocolate Agar. J Clin Microbiol. 2008;46:4095-8. [ Links ]

Singh S, Saluja TP, Kaur M, Khilnani GC. Comparative evaluation of FAST Plaque assay with PCR and other conventional in vitro diagnostic methods for the early detection of pulmonary tuberculosis. J Clin Lab Anal. 2008;22:367-74. [ Links ]

Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual nacional de vigilância laboratorial da tuberculose e outras microbactérias. (Ministry of Health. Secretary of Health Surveillance. National Guide for laboratorial surveillance of tuberculosis and other microbacteria). Brasília: Ministério da Saúde; 2008. 436 p.: il. (Série A. Normas e Manuais Técnicos). [ Links ]

Petri Junior WA. Fármacos utilizados na quimioterapia da tuberculose, da doença causada pelo complexo Mycobacterium avium e da lepra (Chemotherapy of Tuberculosis, Mycobacterium avium Complex Disease and Leprosy). In: Gilman AG, Hardman J, Limbird LE. Goodman & Gilman. As Bases Farmacológicas Da Terapêutica (Goodman and Gilman's The Pharmacological Basis of Therapeutics). 10ed. Rio de Janeiro: Mc Graw Hill, 2003. 955-70 p. [ Links ]

Litt JZ. Drug eruptions & reactions manual: D.E.R.M. 18th ed. New York: Informa Healthcare; 2012. [ Links ]

Azulay RD, Azulay DR. Drogas de Grande Valor em Terapêutica Dermatológica (Drugs of great value in dermatological therapy). In: Azulay DR. Dermatologia. 5. ed. Rio de Janeiro: Guanabara Koogan; 2011. p.872-910. [ Links ]

Financial Support: None

How to cite this article: Dias MFRG, Bernardes Filho F, Quaresma MV, Nascimento LV, Nery JAC, Azulay DR. Update on cutaneous tuberculosis. An Bras Dermatol. 2014;89(6):925-38.

*Work performed at Professor Rubem David Azulay Dermatology Institute- Rio de Janeiro Santa Casa da Misericórdia Hospital (IDPRDA-SCMRJ) - Rio de Janeiro (RJ), Brazil.

ErratumDr. Leninha Valério do Nascimento was not co-author of the article “Atualização em tuberculose cutânea/ Update on cutaneous tuberculosis” , published in journal 89(6), p.925-38

Received: July 21, 2013; Accepted: September 26, 2013

MAILING ADDRESS: Maria Fernanda Reis Gavazzoni Dias, Rua Mariz e barros, 176 salas 607 e 608, Icaraí, 24220-121 - Niterói - RJ, Brazil. E-mail:

Conflict of Interest: None

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