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Skin Tuberculosis in Children: Learning from India
Dermatol Clin 26 (2008) 285–294
Skin Tuberculosis in Children: Learning from India Gomathy Sethuraman, MD, MNAMSa,b,*, V. Ramesh, MDc, M. Ramam, MDa, Vinod K. Sharma, MD, MNAMSa a
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi 110029, India b Division of Pediatric Dermatology, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago IL 60614, USA c Department of Dermatology, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India
Tuberculosis is one of the major health problems in India. India is the most tuberculosisburdened country, with an incidence of 1.8 million cases per annum [1]. Many factors contribute to this burden, including poor living conditions, overcrowding, poverty, malnutrition, illiteracy, and others. The rapid spread of HIV infection during the last decade is an added problem. Childhood tuberculosis represents 5% to 15% of all cases of tuberculosis. Pulmonary tuberculosis is the most common form and extrapulmonary tuberculosis is seen in 20% of children [2]. Cutaneous tuberculosis accounts for about 1.5% of extrapulmonary tuberculosis [3]. Cutaneous tuberculosis can have varied manifestations in children. This article focuses mainly on cutaneous tuberculosis in the Indian pediatric population. Epidemiology Cutaneous tuberculosis is caused by Mycobacterium tuberculosis and rarely by Mycobacterium bovis and the bacille Calmette-Gu_erin (BCG), an attenuated strain of M bovis [4]. The incidence of cutaneous tuberculosis in India is approximately 0.1% of the total dermatology out-patient department [5–7], in contrast to studies from Hong Kong where the figure is 0.066% to 0.04% of new dermatology cases [8,9]. The prevalence of cutaneous tuberculosis in children varies, from 18.7% of all cases of skin tuberculosis in Chandigarh [10], * Corresponding author. Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi 110029, India. E-mail address: [email protected] (G. Sethuraman).
to 20.4% in Varanasi [11], 24.41% in Chennai [6], and 31.7% in Delhi [12]. The highest prevalence, 47.9% [13] and 53.9 % [3], has recently been reported in two large series from Delhi. In the recent series by Vashist and colleagues [3], 75 children under 14 years old, with different forms of cutaneous tuberculosis, were seen over a period of 18 months. In a similar study by Pandhi and colleagues [13] in 2004, 68 children were seen over a 15-month period. These shorter periods of time are in contrast to earlier series by Kumar and colleagues [10], who described 75 cases over a long period of 25 years, and Ramesh and colleagues [12], who reported 63 cases taking place during 7 years, which suggests that tuberculosis may be prevalent in some pockets of north India. Most cutaneous tuberculosis is seen in the age group of 10 to14 years [10,13]. The occurrence of cutaneous tuberculosis has no significant male or female preponderance. However, scrofuloderma tends to occur more commonly in girls [10,13]. The two most common forms of skin tuberculosis reported in India are scrofuloderma and lupus vulgaris [2,3,10–12]. In recent reports, tuberculids (mainly lichen scrofulosorum) is the second most common form of cutaneous tuberculosis [3,13]. Underlying systemic involvement is common in children compared with adults. It can be seen in 12.7% to 53.4% of the children with different cutaneous tuberculosis, more so with scrofuloderma [3,10,12,13]. Tuberculous lymphadenitis is the most common involvement, seen in 29.2% [7]. Pulmonary infection is seen in 12.6% to 20%, bone infection in 5.8% to 10%, and abdominal tuberculosis in 5.8% of the children [3]. Multiple patterns of cutaneous tuberculosis are often reported
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in children (around 5%). Scrofuloderma can occur in association with lupus vulgaris, tuberculosis verrucosa cutis, and lichen scrofulosorum [10,12,14,15]. The BCG vaccine is protective against disseminated tuberculosis. It has also been shown that it offers moderate protection against cutaneous tuberculosis [16]. One study found that children who had been vaccinated did not have disseminated disease and three children in the unvaccinated group had disseminated disease [10]. Others did not find any significant differences between the vaccinated and the unvaccinated groups [12]. Table 1 summarizes the different clinical patterns of cutaneous tuberculosis in five different series. Pathogenesis and classification Children acquire the infection from infected adults. Initially, they develop a primary infection,
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mostly in the lungs and sometimes in the skin or mucosa, along with regional lymphadenopathy. Sometimes, it can spread further by way of the lymphatics or the blood stream. Most of the time, the primary infection goes to the latent stage, where the organisms remain dormant. Reactivation of infection occurs at any point of time when the condition becomes favorable for the bacilli. Exogenous reinfection may also occur in patients with healed infection after many years, especially in the regions of high prevalence. In true cutaneous tuberculosis, the bacilli reach the skin either from the exogenous or endogenous focus [17]. None of the many classification systems of cutaneous tuberculosis are satisfactory. The simple working classification in children includes true tuberculosis and tuberculids. The former is further subclassified into primary and secondary, depending on previous sensitization or exposure (Box 1).
Table 1 Clinical patterns of childhood tuberculosis in different Indian series
Sample size Study period Clinical types SFD LV TBVC Gumma Tuberculids LSF PNT Multiple patterns Sites of involvement SFD LV Systemic involvement Histologic correlation AFB: histology AFB: cytology AFB: culture Mantoux reactivity HIV
Latika et al [14] 1999 (Delhi)
Ramesh et al [12] 1999 (Delhi)
Kumar et al [10] 2000 (Chandigarh)
Pandhi et al [13] 2004 (Delhi)
Vashist et al [3] 2007 (Delhi)
20a 1y
63 7y
75 25 y
68 15 mo
103 18 mo
8 (40.0%) 10 (50.0%) 3 (15.0%) 0
23 (36.5%)b 40 (63.5%)c d d
40 (53.3%) 30 (40.0%) 3 (4.0%) 1 (1.3%)
30 (44.1%) 15 (22.1%) 3 (44.0%) 0
38 (36.9%) 22 (21.3%) 4 (3.9%) 0
2 (15.0%) 0 3
0 0 1
1 0 NA
16 (23.5%) 0 4
34 (33.0%) 4 5
d d d
Neck Lower limbs 8 (12.7%)
Neck Face, lower limb 16 (21.3%)
Neck Face, lower limbs 26 (38.2%)
Neck Lower limbs 55 (53.4%)
20 (100.0%)
NA
48 (64.0%)
54 (80.6%)
73 (70.9%)
0 NA 1 (5.0%) 20 (100.0%) 0
3 (4.7%) NA 4 (6.3%) 62 (98.4%) 0 (tested in 5)
13 (17.3%) NA NA 61 (85.9%) NA
2 (2.9%) 7 (10.3%) 6 (8.8%) 66 (97.1%) 0
17 19 11 68 0
(16.5%) (18.4%) (10.7%) (66.0%)
In a recent series of tuberculosis (adults and children) from Chennai [6], 52 were children under 12; 26 had lupus vulgaris, 14 had tuberculosis verrucosa cutis, and 12 had scrofuloderma. Abbreviations: AFB, acid-fast bacilli; LSF, lichen scrofulosorum; LV, lupus vulgaris; NA, not available; PNT, papulonecrotic tuberculid; SFD, scrofuloderma; TBVC, tuberculosis verrucosa cutis. a One patient had concomitant lupus vulgaris and scrofuloderma; of the two cases of lichen scrofulosorum, one had coexisting tuberculosis verrucosa cutis and one had scrofuloderma. b Four children had associated scrofulous gumma. c Tuberculosis verrucosa cutis was considered the hypertrophic type of lupus vulgaris, which was seen in 11 children.
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Box 1. Classification of cutaneous tuberculosis True tuberculosis Primary tuberculosis Tuberculous chancre Miliary tuberculosis Secondary tuberculosis Scrofuloderma Lupus vulgaris Tuberculosis verrucosa cutis Tuberculous metastatic abscess (gumma) Orificial tuberculosis Tuberculids Lichen scrofulosorum Papulonecrotic tuberculid Scrofuloderma The most common form of cutaneous tuberculosis in children is scrofuloderma [3,10,13]. It appears to be more severe in children, compared with adults. It is usually unilateral and results from the direct invasion of the tubercle bacilli
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into the skin from an underlying tuberculous focus, which is most often the lymph nodes. The cervical group of lymph nodes is commonly affected, which is probably because of the consumption of unpasteurized or unboiled milk in many parts of the country [10]. The other groups of lymph nodes that can be involved are axillary, inguinal, parasternal, epitrochlear, pre- and postauricular, submandibular, occipital, and supraclavicular nodes. Scrofuloderma also occurs secondary to infection in the bones, joints, and testes [18,19]. Scrofuloderma usually starts as subcutaneous nodules or swelling, leading to the formation of cold abscesses, which, over a period of months, rupture to form the sinus tracts or ulceration. The ulcers are typically shallow and undermined with bluish margins. Spontaneous resolution may occur after many months or years, healing with the characteristic puckered scar. Widespread localized lesions sometimes present as multiple swellings and ulcers with irregular, finger-like scrofulous extension involving a large area (Fig. 1A, B) [12]. Multifocal lesions involving axillary, inguinal, and other bony areas [16], and symmetric scrofuloderma from an underlying bony focus on both ankles have been reported (see Fig. 1C) [15].
Fig. 1. (A) Scrofuloderma. (B) Scrofulous gumma. (C) Symmetric scrofuloderma with warty tuberculosis.
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The tuberculin test is usually positive. Biopsy from the periphery of the lesion will demonstrate a tuberculoid granuloma with considerable necrosis and inflammation. The organisms can be demonstrated in the biopsy or smear [20]. Lupus vulgaris Lupus vulgaris is the most common form of cutaneous tuberculosis in adults [10]. It usually
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occurs in previously sensitized individuals. It begins as asymptomatic, infiltrating papules and plaques. The lesions slowly spread and can affect a large area of the body. Typically, the lesion is a well-demarcated, skin-colored or erythematous plaque with deep-seated, tiny nodules that can be seen as yellow-brown macules on diascopy. Healing and scarring in one area and activity in another is the hallmark of lupus vulgaris (Fig. 2A). In children, the lower extremities and
Fig. 2. (A) Lupus vulgaris showing the classic plaque type. (B, C, D) Multifocal lupus vulgaris including the mucosa. (E) Lupus vulgaris involving the knees, with contracture.
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gluteal region are the commonly affected sites [3,12–14]. Many clinical variants have been described: (1) the classic plaque or the keratotic type, (2) the hypertrophic form, (3) the ulcerative form, (4) the atrophic form, and (5) the mutilating form. Of these, the plaque or the keratotic type is the most common form reported [12]. Many unusual clinical variants have been described. Multifocal (Fig. 2B–D) and symmetric lupus vulgaris affecting the knees, possibly caused by exogenous inoculation of the organism, has been reported [21]. Sporotrichoid pattern due to lymphatic spread is rare [22]. Lupus vulgaris may develop in the vicinity of a scrofuloderma lesion. In scrofuloderma, a persistent, suppurative sinus discharge rich in organisms is present and the adjoining skin is infected because of autoinoculation, resulting in lupus vulgaris [11]. It may also develop on the healed areas of scrofuloderma [18]. Rarely, lupus vulgaris may develop following BCG vaccination. Involvement of the mucous membrane is rare. It is usually involved as an extension of the skin lesions (see Fig. 2C). Lupus vulgaris can affect the genitalia in both boys and girls, which may lead to serious consequences because of its chronicity [12]. Lupus vulgaris around the joints may lead to contractures (Fig. 2E). Histopathology shows tuberculoid granulomas with epithelioid cells and Langhans giant cells, along with epidermal changes. Necrosis is usually not seen. The granulomatous process may destroy the appendages. Fibrosis may be seen in the areas of scarring and healing. Organisms are scanty and may be difficult to demonstrate [20]. Tuberculosis verrucosa cutis Tuberculosis verrucosa cutis, otherwise known as warty tuberculosis, occurs as a result of exogenous inoculation tuberculosis in previously sensitized individuals. It typically occurs on the lower extremities, especially the acral areas, and it may be unilateral or bilateral. It begins as a small verrucous papule, which slowly extends to form large irregular verrucous plaques. The surface may show deep fissures or clefts that may extrude pus and perilesional erythema is often present. The lesion may persist for many years and progress slowly [18,20]. At times, it is difficult to distinguish it from the hypertrophic variant of lupus vulgaris and hence, it can be considered a variant of lupus vulgaris. Histologically, the condition involves massive pseudoepitheliomatous hyperplasia and granulomatous
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infiltrate with necrosis. Acid-fast bacilli can be demonstrated in the tissue [20].
Acute miliary tuberculosis Acute miliary tuberculosis is rare in India. Only a few cases in younger children have been reported [23,24]. It is caused by the hematogenous dissemination of the organism. Usually, internal involvement is widespread, affecting the lungs and meninges. The cutaneous lesions consist of widespread erythematous papules, pustules, purpura, and, rarely, umbilicated vesicles. Sometimes, neonates born to tuberculous mothers develop a milder form of the disease, with limited visceral involvement and only a few scattered papules. The tuberculin test is usually negative [4]. Histologically, it shows numerous microabscesses containing neutrophils and numerous organisms that may be surrounded by macrophages and giant cells [20].
Tuberculous metastatic abscess Tuberculous gumma, or the metastatic abscess, has been reported in only one case from Chandigarh [10] and three cases from Delhi [12]. It is usually seen in malnourished or immunosuppressed children. It results from a disseminated infection from a hematogenous route and presents as multiple dermal or subcutaneous nodules that break down to form necrotic ulcer and fistulous tracts (Fig. 1B, Fig. 3). Histologically, it shows massive necrosis with copious amounts of mycobacteria [20].
Fig. 3. Tuberculous gumma of the face.
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Primary tuberculous chancre Tuberculous chancre, otherwise known as primary inoculation tuberculosis or tuberculous primary complex, is rare and is mostly seen in high endemic areas. It consists of the tuberculous chancre and associated regional lymphadenopathy, and it results from the inoculation of the organisms in previously unsensitized persons. The organisms are usually introduced at the site of minor injury or abrasion. Skin lesions start around 4 weeks after the inoculation. The lesion starts as an asymptomatic papule that ulcerates. The ulcer is usually shallow, with granulomatous base and undermined bluish margins, which might heal after some time. The organisms may remain dormant and may get reactivated later. Regional lymphadenopathy develops 3 to 8 weeks after the infection. Sometimes, abscesses may form at the puncture wounds. Inoculation of the finger may manifest as paronychia [4,25]. Orificial tuberculosis Tuberculosis cutis orificialis presents as shallow, granulomatous ulcer in and around the mucosal orifices, usually the mouth and anus. It is caused by autoinoculation of the organism in patients who have advanced internal tuberculosis [20]. Unusual patterns of tuberculosis Sporotrichoid tuberculosis The sporotrichoid pattern is seen in 3% of all patients who have cutaneous tuberculosis, and it is mostly reported in children. Lupus vulgaris, scrofuloderma, and tuberculosis verrucosa cutis can present in this pattern. It occurs by lymphatic spread and is characterized by linear lesions confined to the same limb (Fig. 4). Cord-like thickening of the lymphatics in between the lesions may occur, which, at times, can be confused with sporotrichosis; but the presence of enlarged regional lymph nodes or ulceration favors tuberculosis [22,26,27].
Fig. 4. Sporotrichoid tuberculosis.
Tuberculous dactylitis Tuberculous dactylitis presents as granulomatous swelling of the finger, most often the index or middle finger. It is always associated with an underlying bony involvement, especially in the proximal phalanges [10,30]. Orofacial tuberculosis Orofacial tuberculosis is part of the differential diagnoses for orofacial granulomatosis (especially in India), which is a nonspecific descriptive term used for various conditions characterized by persistent swelling of the orofacial tissues showing noncaseating granulomas [31,32]. The important clue to the diagnosis of tuberculosis is that the biopsy in these cases demonstrates caseating granulomas, which is further supported by the Mantoux test. It usually starts as a papule or plaque in the oral area or as swelling of the upper lip, which, over a course of time, extends into the oral mucosa, including the tongue and nose. If untreated, it can to lead to severe mutilation and complications like destruction of the nasal septum, and involvement of the palate, nasolacrimal duct, and middle ear.
Inverse sporotrichoid pattern The inverse sporotrichoid pattern, or segmental form, with involvement of the proximal half of the lower limb caused by retrograde lymphatic spread from the inguinal lymph nodes, has also been described [28,29].
Tuberculids Tuberculids are delayed sensitivity reactions to M tuberculosis in patients with a strong immune response. The criteria include absence of organisms in the smear and negative culture, strong
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Mantoux reaction, and resolution of the lesions with antituberculous treatment. Tuberculids include lichen scrofulosorum and papulonecrotic tuberculid, in which the organisms significantly contribute to the disease process. In facultative tuberculids, the mycobacterium is one of the many causative factors and consist of erythema induratum and erythema nodosum. Other conditions, like rosacea-like tuberculid, lupus miliaris disseminatus faciei, and lichenoid tuberculid, are no longer considered to be tuberculids [4]. Lichen scrofulosorum Lichen scrofulosorum is commonly seen in children and young adults. In a series of 39 patients with lichen scrofulosorum, 82% were younger than 15 years of age [33]. It has been reported in a significant number of patients during the last few years. In recent reports by Pandhi and colleagues [13] and Vashist and colleagues [3], lichen scrofulosorum was the second most common pattern seen in 23.5% and 33% of cases, respectively. It usually indicates an underlying tuberculous focus in the lymph nodes, especially the cervical, hilar, and mediastinal nodes, bones, and sometimes lungs. Rarely, it can be seen in association with tuberculous meningitis and miliary tuberculosis [33,34]. The underlying tuberculous infection has been documented in two series, in 73.5% and 87.5% of
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the cases, respectively [3,13]. It usually presents as asymptomatic yellow, brown, or lichenoid, firm, follicular papules on the trunk (Fig. 5). The lesions may be flat topped or spiny with scaling. Histologically, the infection shows well-formed superficial granulomas around the follicles [3].
Papulonecrotic tuberculids These lesions consist of symmetric eruptions of necrotizing papules on the extensor aspect of the extremities and buttocks. Histologically, papulonecrotic tuberculids show features of vasculitis and a wedge-shaped area of necrosis. Nonspecific infiltrates or tuberculoid granuloma may be seen surrounding the necrosis [4].
Erythema nodosum Erythema nodosum consists of painful subcutaneous nodules, mostly on the extremities (shins), accompanied by fever and constitutional symptoms. The lesions usually last for about 2 weeks. Biopsy shows septal panniculitis without vasculitis and usually, no granuloma is seen. Erythema nodosum is most often caused by streptococcal infections, drug reactions, and sarcoidosis. But in India, tuberculosis still remains an important cause. However, children are rarely affected [3,35].
Fig. 5. Lichen scrofulosorum.
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Erythema induratum Erythema induratum is almost never encountered in children. The clinical manifestations include recurrent, painful subcutaneous nodules occurring on the posterior leg, which break down into slowly healing deep ulcers with bluish margins. It heals with atrophic scars. Generally, there is no systemic involvement. Biopsy shows lobular panniculitis with vasculitis. The later stage includes granulomatous inflammation consisting of histiocytes and giant cells, and sometimes, caseous necrosis [4].
HIV and cutaneous tuberculosis In patients who have HIV infection, the presentations of cutaneous tuberculosis may be severe and include miliary tuberculosis, tuberculous ulcers, and papulonecrotic tuberculid [36]. In a series of 231 patients (both adults and children) with cutaneous tuberculosis from Chennai, South India, only 2 patients were HIV positive [6].
Complications of BCG vaccination BCG vaccine is a live, freeze-dried vaccine derived from an attenuated strain of M bovis (BCG). It is given routinely to all infants at risk of early exposure to tuberculosis. It should be given soon after the child is born (in India). The vaccination dose is 0.05 mL and is administered intradermally with a tuberculin syringe. Usually, 2 weeks after vaccination, a small papule develops which, over a period of 6 weeks, enlarges and ulcerates. It heals with a scar. Nonspecific complications such as keloid, eczema, maculopapular rash, erythema nodosum, infections, poor healing, ulceration, and abscess formation can occur after the vaccination. The specific complications include development of lupus vulgaris, verrucous tuberculosis, tuberculous chancre, lymphadenitis, and Koch phenomenon. Disseminated BCG infection, tuberculids, and other organ involvement may also occur [4].
Diagnosis The diagnosis is usually based on the characteristic clinical morphology and laboratory testing. In addition to the routine laboratory evaluation, all children should be evaluated for underlying systemic tuberculosis [37]. The Mantoux or tuberculin
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test is a good screening tool to detect for the presence or absence of tuberculosis infection. It can be positive in 80% (V. Ramesh, MD and M. Ramam, MD, unpublished data) of the children with different forms of cutaneous tuberculosis, more often with localized disease. It is performed by injecting 0.1 mL (5 TU) of the purified protein derivative (PPD RT23) on the volar surface of the forearm. Induration of 10 mm or more is considered significant and only indicates infection and not necessarily disease. Induration may also be caused by environmental mycobacteria and BCG sensitivity, in which case the induration will be less than 10 mm. Absence of reaction signifies a negative test [38]. The gold standard for the diagnosis of cutaneous tuberculosis is the direct demonstration of the organism either in a tissue smear or biopsy, or by isolation in culture. But it may be difficult in paucibacillary cases because of the scanty number of organisms. It has been identified in the biopsy sections of scrofuloderma and lupus vulgaris in 36.8% and 13.6% of cases, respectively [3]. In a cytology specimen it can be demonstrated in 39.5% and 18.2% of cases [3]. Culturing the organisms in the Lowenstein-Jenson medium may be tedious and the positivity is found in 18.4% in scrofuloderma and 12.5% in lupus vulgaris cases [3]. But with improved techniques using multiple media, and the use of Kirchner’s liquid medium for storage of the tissue, the culture positivity will be better. In a recent report from Chennai, the organism was isolated in 55% of cases [6]. The clinicohistologic correlation can be seen in 64% to 80.6% of cases of cutaneous tuberculosis in children [3,13]. The histopathologic correlation is found in 47% to 65.7% of cases of scrofuloderma and 73% to 80% of cases of lupus vulgaris [3,13]. The development of polymerase chain reaction (PCR) to identify the infectious agents has increased considerably the sensitivity of the diagnosis of cutaneous tuberculosis, especially in paucibacillary cases. The combination of hybridization with PCR will further increase the sensitivity and specificity of PCR [39]. A therapeutic trial of antituberculous drugs may be a useful diagnostic tool in developing countries like India. A four-drug regimen (HRZE) is usually given over a period of 6 weeks. Considerable response at the end of 6 weeks would appear to prove the diagnosis of cutaneous tuberculosis [40]. Patients who have not responded by this time are unlikely to do so with further treatment and their diagnosis should be reviewed [41].
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Treatment Cutaneous tuberculosis can be treated with the standard regime used for pulmonary tuberculosis. It consists of the initial 2 months intensive phase with four drugs (rifampicin [8–12 mg/kg], isoniazid [INH] [4–6 mg/kg], pyrazinamide [20–30 mg/kg], and ethambutol [15–20 mg/kg]), followed by 4 months of continuation therapy with two drugs (rifampicin and INH) (2 HRZE/4HR). Some investigators do not use ethambutol in children younger than 5 years because of ocular toxicity, but it can be used with proper monitoring. Patients with extensive skin involvement and the underlying systemic disease may need a longer period of treatment. Currently, the treatment of cutaneous tuberculosis is by the directly observed treatment, short course strategy, implemented by the World Health Organization. This program has been fully adopted by the revised national tuberculosis control program of the Government of India. According to these guidelines, cutaneous tuberculosis is classified as category III, which is treated with three drugs, rifampicin, INH, and pyrazinamide, given thrice weekly for the first 2 months, followed by two drugs, rifampicin and INH, for the following 4 months. When the lesions are extensive, or when more than one group of lymph nodes are involved in scrofuloderma, then the category I regime can be given (2 HRZE/4HR). Summary Cutaneous tuberculosis in children is a major health problem in India. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis. However, the trend in the pattern of cutaneous tuberculosis is changing, as the tuberculid, lichen scrofulosorum, has become more common in recent years. Overall, the clinical patterns are comparable with adults. However, children can have widespread and severe involvement because many unusual and uncommon patterns are known to occur in children. Underlying systemic involvement is more common in children, compared with adults. References [1] WHO. Global tuberculosis control-surveillance, planning, financing. Geneva (Switzerland): World Health Organization; 2006.
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[20] Lucas S. Bacterial diseases. In: Elderly, editor. Lever’s histopathology of the skin. Philadelphia: Lippincott-Ravens; 1997. p. 468–77. [21] Sethuraman G, Thappa DM, Kurvilla S. Symmetrical reinfection lupus vulgaris. Pediatr Dermatol 1999;16:488–90. [22] Ramesh V. Sporotrichoid tuberculosis. Clin Exp Dermatol 2007;32:680–2. [23] Raut WK, Sawaiti VK, Bobhate SK, et al. Acute miliary tuberculosis of the skin: a case report and review of literature. Indian J Dermatol 2002;47: 57–9. [24] Sangeeta AT, Sad R. Unusual cutaneous ulcers in miliary tuberculosis. Indian J Dermatol Venereol Leprol 1993;59:24–6. [25] Pillai SM, Shanmugam, Sarojini PA. Primary inoculation tuberculosis. Indian J Dermatol Venereol Leprol 1988;54:97–8. [26] Khandpur S, Nanda S, Reddy BS. An unusual episode of lupus vulgaris masquerading as sporotrichosis. Int J Dermatol 2001;40:336–9. [27] Suvasini Sharma, Choudhary Ramesh, Monica Juneja, et al. Cutaneous tuberculosis mimicking sporotrichosis. Indian J Pediatr 2005;72:86–8. [28] Hanumanthappa H. Segmental tuberculosis verrucosa cutis. Indian J Dermatol Venereol Leprol 1994;60:37. [29] Singhal A, Mehta S, Bhattacharya SN. Tuberculous gumma in inverse sporotrichoid pattern. Indian J Dermatol 2006;50:S46–7. [30] Kothari PR, Shankar G, Gupta A, et al. Disseminated spina ventosa. Indian J Chest Dis Allied Sci 2004;46:295–6. [31] Alawi F. Granulomatous diseases of the oral tissues: differential diagnosis and update. Dent Clin North Am 2005;49:203–21.
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[32] Lea˜o JC, Hodgson T, Scully C, et al. Orofacial granulomatosis. Aliment Pharmacol Ther 2004;20:1019–27. [33] Singhal A, Bhattacharya SN. Lichen scrofulosorum: a prospective study of 39 patients. Int J Dermatol 2005;44:489–93. [34] Beena KR, Ramesh V, Mukherjee A. Lichen scrofulosorum – a series of eight cases. Dermatology 2000; 201:272–4. [35] Sarveshwari KN, Swamikannu M, Ramakrishnan S. An etiological analysis of erythema nodosum in a community hospital. Indian J Dermatol Venereol Leprol 2001;67:287–9. [36] Hay RJ. Cutaneous infection with Mycobacterium tuberculosis: how has this altered with the changing epidemiology of tuberculosis? Curr Opin Infect Dis 2005;18:93–5. [37] Ramesh V, Misra RS, Jain RK. Secondary tuberculosis of the skin. Clinical features and problems in laboratory diagnosis. Int J Dermatol 1987;26: 578–81. [38] Aggarwal A, Guglani L, Faridi MMA. Standardization of Mantoux test. Indian Pediatr 2002;39: 404–6. [39] Arora SK, Kumar B, Sehgal S. Development of a polymerase chain reaction dot-blotting system for detecting cutaneous tuberculosis. Br J Dermatol 2000;142:72–6. [40] Ramam M, Mittal R, Ramesh V. How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis. Int J Dermatol 2005;44:121–4. [41] Ramam M, Tejasvi T, Manchanda Y, et al. What is the appropriate duration of a therapeutic trial in cutaneous tuberculosis? Further observations. Indian J Dermatol Venereol Leprol 2007;73:243–6.
Skin Tuberculosis in Children: Learning from India Gomathy Sethuraman, MD, MNAMSa,b,*, V. Ramesh, MDc, M. Ramam, MDa, Vinod K. Sharma, MD, MNAMSa a
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi 110029, India b Division of Pediatric Dermatology, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago IL 60614, USA c Department of Dermatology, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India
Tuberculosis is one of the major health problems in India. India is the most tuberculosisburdened country, with an incidence of 1.8 million cases per annum [1]. Many factors contribute to this burden, including poor living conditions, overcrowding, poverty, malnutrition, illiteracy, and others. The rapid spread of HIV infection during the last decade is an added problem. Childhood tuberculosis represents 5% to 15% of all cases of tuberculosis. Pulmonary tuberculosis is the most common form and extrapulmonary tuberculosis is seen in 20% of children [2]. Cutaneous tuberculosis accounts for about 1.5% of extrapulmonary tuberculosis [3]. Cutaneous tuberculosis can have varied manifestations in children. This article focuses mainly on cutaneous tuberculosis in the Indian pediatric population. Epidemiology Cutaneous tuberculosis is caused by Mycobacterium tuberculosis and rarely by Mycobacterium bovis and the bacille Calmette-Gu_erin (BCG), an attenuated strain of M bovis [4]. The incidence of cutaneous tuberculosis in India is approximately 0.1% of the total dermatology out-patient department [5–7], in contrast to studies from Hong Kong where the figure is 0.066% to 0.04% of new dermatology cases [8,9]. The prevalence of cutaneous tuberculosis in children varies, from 18.7% of all cases of skin tuberculosis in Chandigarh [10], * Corresponding author. Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi 110029, India. E-mail address: [email protected] (G. Sethuraman).
to 20.4% in Varanasi [11], 24.41% in Chennai [6], and 31.7% in Delhi [12]. The highest prevalence, 47.9% [13] and 53.9 % [3], has recently been reported in two large series from Delhi. In the recent series by Vashist and colleagues [3], 75 children under 14 years old, with different forms of cutaneous tuberculosis, were seen over a period of 18 months. In a similar study by Pandhi and colleagues [13] in 2004, 68 children were seen over a 15-month period. These shorter periods of time are in contrast to earlier series by Kumar and colleagues [10], who described 75 cases over a long period of 25 years, and Ramesh and colleagues [12], who reported 63 cases taking place during 7 years, which suggests that tuberculosis may be prevalent in some pockets of north India. Most cutaneous tuberculosis is seen in the age group of 10 to14 years [10,13]. The occurrence of cutaneous tuberculosis has no significant male or female preponderance. However, scrofuloderma tends to occur more commonly in girls [10,13]. The two most common forms of skin tuberculosis reported in India are scrofuloderma and lupus vulgaris [2,3,10–12]. In recent reports, tuberculids (mainly lichen scrofulosorum) is the second most common form of cutaneous tuberculosis [3,13]. Underlying systemic involvement is common in children compared with adults. It can be seen in 12.7% to 53.4% of the children with different cutaneous tuberculosis, more so with scrofuloderma [3,10,12,13]. Tuberculous lymphadenitis is the most common involvement, seen in 29.2% [7]. Pulmonary infection is seen in 12.6% to 20%, bone infection in 5.8% to 10%, and abdominal tuberculosis in 5.8% of the children [3]. Multiple patterns of cutaneous tuberculosis are often reported
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in children (around 5%). Scrofuloderma can occur in association with lupus vulgaris, tuberculosis verrucosa cutis, and lichen scrofulosorum [10,12,14,15]. The BCG vaccine is protective against disseminated tuberculosis. It has also been shown that it offers moderate protection against cutaneous tuberculosis [16]. One study found that children who had been vaccinated did not have disseminated disease and three children in the unvaccinated group had disseminated disease [10]. Others did not find any significant differences between the vaccinated and the unvaccinated groups [12]. Table 1 summarizes the different clinical patterns of cutaneous tuberculosis in five different series. Pathogenesis and classification Children acquire the infection from infected adults. Initially, they develop a primary infection,
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mostly in the lungs and sometimes in the skin or mucosa, along with regional lymphadenopathy. Sometimes, it can spread further by way of the lymphatics or the blood stream. Most of the time, the primary infection goes to the latent stage, where the organisms remain dormant. Reactivation of infection occurs at any point of time when the condition becomes favorable for the bacilli. Exogenous reinfection may also occur in patients with healed infection after many years, especially in the regions of high prevalence. In true cutaneous tuberculosis, the bacilli reach the skin either from the exogenous or endogenous focus [17]. None of the many classification systems of cutaneous tuberculosis are satisfactory. The simple working classification in children includes true tuberculosis and tuberculids. The former is further subclassified into primary and secondary, depending on previous sensitization or exposure (Box 1).
Table 1 Clinical patterns of childhood tuberculosis in different Indian series
Sample size Study period Clinical types SFD LV TBVC Gumma Tuberculids LSF PNT Multiple patterns Sites of involvement SFD LV Systemic involvement Histologic correlation AFB: histology AFB: cytology AFB: culture Mantoux reactivity HIV
Latika et al [14] 1999 (Delhi)
Ramesh et al [12] 1999 (Delhi)
Kumar et al [10] 2000 (Chandigarh)
Pandhi et al [13] 2004 (Delhi)
Vashist et al [3] 2007 (Delhi)
20a 1y
63 7y
75 25 y
68 15 mo
103 18 mo
8 (40.0%) 10 (50.0%) 3 (15.0%) 0
23 (36.5%)b 40 (63.5%)c d d
40 (53.3%) 30 (40.0%) 3 (4.0%) 1 (1.3%)
30 (44.1%) 15 (22.1%) 3 (44.0%) 0
38 (36.9%) 22 (21.3%) 4 (3.9%) 0
2 (15.0%) 0 3
0 0 1
1 0 NA
16 (23.5%) 0 4
34 (33.0%) 4 5
d d d
Neck Lower limbs 8 (12.7%)
Neck Face, lower limb 16 (21.3%)
Neck Face, lower limbs 26 (38.2%)
Neck Lower limbs 55 (53.4%)
20 (100.0%)
NA
48 (64.0%)
54 (80.6%)
73 (70.9%)
0 NA 1 (5.0%) 20 (100.0%) 0
3 (4.7%) NA 4 (6.3%) 62 (98.4%) 0 (tested in 5)
13 (17.3%) NA NA 61 (85.9%) NA
2 (2.9%) 7 (10.3%) 6 (8.8%) 66 (97.1%) 0
17 19 11 68 0
(16.5%) (18.4%) (10.7%) (66.0%)
In a recent series of tuberculosis (adults and children) from Chennai [6], 52 were children under 12; 26 had lupus vulgaris, 14 had tuberculosis verrucosa cutis, and 12 had scrofuloderma. Abbreviations: AFB, acid-fast bacilli; LSF, lichen scrofulosorum; LV, lupus vulgaris; NA, not available; PNT, papulonecrotic tuberculid; SFD, scrofuloderma; TBVC, tuberculosis verrucosa cutis. a One patient had concomitant lupus vulgaris and scrofuloderma; of the two cases of lichen scrofulosorum, one had coexisting tuberculosis verrucosa cutis and one had scrofuloderma. b Four children had associated scrofulous gumma. c Tuberculosis verrucosa cutis was considered the hypertrophic type of lupus vulgaris, which was seen in 11 children.
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Box 1. Classification of cutaneous tuberculosis True tuberculosis Primary tuberculosis Tuberculous chancre Miliary tuberculosis Secondary tuberculosis Scrofuloderma Lupus vulgaris Tuberculosis verrucosa cutis Tuberculous metastatic abscess (gumma) Orificial tuberculosis Tuberculids Lichen scrofulosorum Papulonecrotic tuberculid Scrofuloderma The most common form of cutaneous tuberculosis in children is scrofuloderma [3,10,13]. It appears to be more severe in children, compared with adults. It is usually unilateral and results from the direct invasion of the tubercle bacilli
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into the skin from an underlying tuberculous focus, which is most often the lymph nodes. The cervical group of lymph nodes is commonly affected, which is probably because of the consumption of unpasteurized or unboiled milk in many parts of the country [10]. The other groups of lymph nodes that can be involved are axillary, inguinal, parasternal, epitrochlear, pre- and postauricular, submandibular, occipital, and supraclavicular nodes. Scrofuloderma also occurs secondary to infection in the bones, joints, and testes [18,19]. Scrofuloderma usually starts as subcutaneous nodules or swelling, leading to the formation of cold abscesses, which, over a period of months, rupture to form the sinus tracts or ulceration. The ulcers are typically shallow and undermined with bluish margins. Spontaneous resolution may occur after many months or years, healing with the characteristic puckered scar. Widespread localized lesions sometimes present as multiple swellings and ulcers with irregular, finger-like scrofulous extension involving a large area (Fig. 1A, B) [12]. Multifocal lesions involving axillary, inguinal, and other bony areas [16], and symmetric scrofuloderma from an underlying bony focus on both ankles have been reported (see Fig. 1C) [15].
Fig. 1. (A) Scrofuloderma. (B) Scrofulous gumma. (C) Symmetric scrofuloderma with warty tuberculosis.
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The tuberculin test is usually positive. Biopsy from the periphery of the lesion will demonstrate a tuberculoid granuloma with considerable necrosis and inflammation. The organisms can be demonstrated in the biopsy or smear [20]. Lupus vulgaris Lupus vulgaris is the most common form of cutaneous tuberculosis in adults [10]. It usually
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occurs in previously sensitized individuals. It begins as asymptomatic, infiltrating papules and plaques. The lesions slowly spread and can affect a large area of the body. Typically, the lesion is a well-demarcated, skin-colored or erythematous plaque with deep-seated, tiny nodules that can be seen as yellow-brown macules on diascopy. Healing and scarring in one area and activity in another is the hallmark of lupus vulgaris (Fig. 2A). In children, the lower extremities and
Fig. 2. (A) Lupus vulgaris showing the classic plaque type. (B, C, D) Multifocal lupus vulgaris including the mucosa. (E) Lupus vulgaris involving the knees, with contracture.
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gluteal region are the commonly affected sites [3,12–14]. Many clinical variants have been described: (1) the classic plaque or the keratotic type, (2) the hypertrophic form, (3) the ulcerative form, (4) the atrophic form, and (5) the mutilating form. Of these, the plaque or the keratotic type is the most common form reported [12]. Many unusual clinical variants have been described. Multifocal (Fig. 2B–D) and symmetric lupus vulgaris affecting the knees, possibly caused by exogenous inoculation of the organism, has been reported [21]. Sporotrichoid pattern due to lymphatic spread is rare [22]. Lupus vulgaris may develop in the vicinity of a scrofuloderma lesion. In scrofuloderma, a persistent, suppurative sinus discharge rich in organisms is present and the adjoining skin is infected because of autoinoculation, resulting in lupus vulgaris [11]. It may also develop on the healed areas of scrofuloderma [18]. Rarely, lupus vulgaris may develop following BCG vaccination. Involvement of the mucous membrane is rare. It is usually involved as an extension of the skin lesions (see Fig. 2C). Lupus vulgaris can affect the genitalia in both boys and girls, which may lead to serious consequences because of its chronicity [12]. Lupus vulgaris around the joints may lead to contractures (Fig. 2E). Histopathology shows tuberculoid granulomas with epithelioid cells and Langhans giant cells, along with epidermal changes. Necrosis is usually not seen. The granulomatous process may destroy the appendages. Fibrosis may be seen in the areas of scarring and healing. Organisms are scanty and may be difficult to demonstrate [20]. Tuberculosis verrucosa cutis Tuberculosis verrucosa cutis, otherwise known as warty tuberculosis, occurs as a result of exogenous inoculation tuberculosis in previously sensitized individuals. It typically occurs on the lower extremities, especially the acral areas, and it may be unilateral or bilateral. It begins as a small verrucous papule, which slowly extends to form large irregular verrucous plaques. The surface may show deep fissures or clefts that may extrude pus and perilesional erythema is often present. The lesion may persist for many years and progress slowly [18,20]. At times, it is difficult to distinguish it from the hypertrophic variant of lupus vulgaris and hence, it can be considered a variant of lupus vulgaris. Histologically, the condition involves massive pseudoepitheliomatous hyperplasia and granulomatous
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infiltrate with necrosis. Acid-fast bacilli can be demonstrated in the tissue [20].
Acute miliary tuberculosis Acute miliary tuberculosis is rare in India. Only a few cases in younger children have been reported [23,24]. It is caused by the hematogenous dissemination of the organism. Usually, internal involvement is widespread, affecting the lungs and meninges. The cutaneous lesions consist of widespread erythematous papules, pustules, purpura, and, rarely, umbilicated vesicles. Sometimes, neonates born to tuberculous mothers develop a milder form of the disease, with limited visceral involvement and only a few scattered papules. The tuberculin test is usually negative [4]. Histologically, it shows numerous microabscesses containing neutrophils and numerous organisms that may be surrounded by macrophages and giant cells [20].
Tuberculous metastatic abscess Tuberculous gumma, or the metastatic abscess, has been reported in only one case from Chandigarh [10] and three cases from Delhi [12]. It is usually seen in malnourished or immunosuppressed children. It results from a disseminated infection from a hematogenous route and presents as multiple dermal or subcutaneous nodules that break down to form necrotic ulcer and fistulous tracts (Fig. 1B, Fig. 3). Histologically, it shows massive necrosis with copious amounts of mycobacteria [20].
Fig. 3. Tuberculous gumma of the face.
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Primary tuberculous chancre Tuberculous chancre, otherwise known as primary inoculation tuberculosis or tuberculous primary complex, is rare and is mostly seen in high endemic areas. It consists of the tuberculous chancre and associated regional lymphadenopathy, and it results from the inoculation of the organisms in previously unsensitized persons. The organisms are usually introduced at the site of minor injury or abrasion. Skin lesions start around 4 weeks after the inoculation. The lesion starts as an asymptomatic papule that ulcerates. The ulcer is usually shallow, with granulomatous base and undermined bluish margins, which might heal after some time. The organisms may remain dormant and may get reactivated later. Regional lymphadenopathy develops 3 to 8 weeks after the infection. Sometimes, abscesses may form at the puncture wounds. Inoculation of the finger may manifest as paronychia [4,25]. Orificial tuberculosis Tuberculosis cutis orificialis presents as shallow, granulomatous ulcer in and around the mucosal orifices, usually the mouth and anus. It is caused by autoinoculation of the organism in patients who have advanced internal tuberculosis [20]. Unusual patterns of tuberculosis Sporotrichoid tuberculosis The sporotrichoid pattern is seen in 3% of all patients who have cutaneous tuberculosis, and it is mostly reported in children. Lupus vulgaris, scrofuloderma, and tuberculosis verrucosa cutis can present in this pattern. It occurs by lymphatic spread and is characterized by linear lesions confined to the same limb (Fig. 4). Cord-like thickening of the lymphatics in between the lesions may occur, which, at times, can be confused with sporotrichosis; but the presence of enlarged regional lymph nodes or ulceration favors tuberculosis [22,26,27].
Fig. 4. Sporotrichoid tuberculosis.
Tuberculous dactylitis Tuberculous dactylitis presents as granulomatous swelling of the finger, most often the index or middle finger. It is always associated with an underlying bony involvement, especially in the proximal phalanges [10,30]. Orofacial tuberculosis Orofacial tuberculosis is part of the differential diagnoses for orofacial granulomatosis (especially in India), which is a nonspecific descriptive term used for various conditions characterized by persistent swelling of the orofacial tissues showing noncaseating granulomas [31,32]. The important clue to the diagnosis of tuberculosis is that the biopsy in these cases demonstrates caseating granulomas, which is further supported by the Mantoux test. It usually starts as a papule or plaque in the oral area or as swelling of the upper lip, which, over a course of time, extends into the oral mucosa, including the tongue and nose. If untreated, it can to lead to severe mutilation and complications like destruction of the nasal septum, and involvement of the palate, nasolacrimal duct, and middle ear.
Inverse sporotrichoid pattern The inverse sporotrichoid pattern, or segmental form, with involvement of the proximal half of the lower limb caused by retrograde lymphatic spread from the inguinal lymph nodes, has also been described [28,29].
Tuberculids Tuberculids are delayed sensitivity reactions to M tuberculosis in patients with a strong immune response. The criteria include absence of organisms in the smear and negative culture, strong
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Mantoux reaction, and resolution of the lesions with antituberculous treatment. Tuberculids include lichen scrofulosorum and papulonecrotic tuberculid, in which the organisms significantly contribute to the disease process. In facultative tuberculids, the mycobacterium is one of the many causative factors and consist of erythema induratum and erythema nodosum. Other conditions, like rosacea-like tuberculid, lupus miliaris disseminatus faciei, and lichenoid tuberculid, are no longer considered to be tuberculids [4]. Lichen scrofulosorum Lichen scrofulosorum is commonly seen in children and young adults. In a series of 39 patients with lichen scrofulosorum, 82% were younger than 15 years of age [33]. It has been reported in a significant number of patients during the last few years. In recent reports by Pandhi and colleagues [13] and Vashist and colleagues [3], lichen scrofulosorum was the second most common pattern seen in 23.5% and 33% of cases, respectively. It usually indicates an underlying tuberculous focus in the lymph nodes, especially the cervical, hilar, and mediastinal nodes, bones, and sometimes lungs. Rarely, it can be seen in association with tuberculous meningitis and miliary tuberculosis [33,34]. The underlying tuberculous infection has been documented in two series, in 73.5% and 87.5% of
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the cases, respectively [3,13]. It usually presents as asymptomatic yellow, brown, or lichenoid, firm, follicular papules on the trunk (Fig. 5). The lesions may be flat topped or spiny with scaling. Histologically, the infection shows well-formed superficial granulomas around the follicles [3].
Papulonecrotic tuberculids These lesions consist of symmetric eruptions of necrotizing papules on the extensor aspect of the extremities and buttocks. Histologically, papulonecrotic tuberculids show features of vasculitis and a wedge-shaped area of necrosis. Nonspecific infiltrates or tuberculoid granuloma may be seen surrounding the necrosis [4].
Erythema nodosum Erythema nodosum consists of painful subcutaneous nodules, mostly on the extremities (shins), accompanied by fever and constitutional symptoms. The lesions usually last for about 2 weeks. Biopsy shows septal panniculitis without vasculitis and usually, no granuloma is seen. Erythema nodosum is most often caused by streptococcal infections, drug reactions, and sarcoidosis. But in India, tuberculosis still remains an important cause. However, children are rarely affected [3,35].
Fig. 5. Lichen scrofulosorum.
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Erythema induratum Erythema induratum is almost never encountered in children. The clinical manifestations include recurrent, painful subcutaneous nodules occurring on the posterior leg, which break down into slowly healing deep ulcers with bluish margins. It heals with atrophic scars. Generally, there is no systemic involvement. Biopsy shows lobular panniculitis with vasculitis. The later stage includes granulomatous inflammation consisting of histiocytes and giant cells, and sometimes, caseous necrosis [4].
HIV and cutaneous tuberculosis In patients who have HIV infection, the presentations of cutaneous tuberculosis may be severe and include miliary tuberculosis, tuberculous ulcers, and papulonecrotic tuberculid [36]. In a series of 231 patients (both adults and children) with cutaneous tuberculosis from Chennai, South India, only 2 patients were HIV positive [6].
Complications of BCG vaccination BCG vaccine is a live, freeze-dried vaccine derived from an attenuated strain of M bovis (BCG). It is given routinely to all infants at risk of early exposure to tuberculosis. It should be given soon after the child is born (in India). The vaccination dose is 0.05 mL and is administered intradermally with a tuberculin syringe. Usually, 2 weeks after vaccination, a small papule develops which, over a period of 6 weeks, enlarges and ulcerates. It heals with a scar. Nonspecific complications such as keloid, eczema, maculopapular rash, erythema nodosum, infections, poor healing, ulceration, and abscess formation can occur after the vaccination. The specific complications include development of lupus vulgaris, verrucous tuberculosis, tuberculous chancre, lymphadenitis, and Koch phenomenon. Disseminated BCG infection, tuberculids, and other organ involvement may also occur [4].
Diagnosis The diagnosis is usually based on the characteristic clinical morphology and laboratory testing. In addition to the routine laboratory evaluation, all children should be evaluated for underlying systemic tuberculosis [37]. The Mantoux or tuberculin
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test is a good screening tool to detect for the presence or absence of tuberculosis infection. It can be positive in 80% (V. Ramesh, MD and M. Ramam, MD, unpublished data) of the children with different forms of cutaneous tuberculosis, more often with localized disease. It is performed by injecting 0.1 mL (5 TU) of the purified protein derivative (PPD RT23) on the volar surface of the forearm. Induration of 10 mm or more is considered significant and only indicates infection and not necessarily disease. Induration may also be caused by environmental mycobacteria and BCG sensitivity, in which case the induration will be less than 10 mm. Absence of reaction signifies a negative test [38]. The gold standard for the diagnosis of cutaneous tuberculosis is the direct demonstration of the organism either in a tissue smear or biopsy, or by isolation in culture. But it may be difficult in paucibacillary cases because of the scanty number of organisms. It has been identified in the biopsy sections of scrofuloderma and lupus vulgaris in 36.8% and 13.6% of cases, respectively [3]. In a cytology specimen it can be demonstrated in 39.5% and 18.2% of cases [3]. Culturing the organisms in the Lowenstein-Jenson medium may be tedious and the positivity is found in 18.4% in scrofuloderma and 12.5% in lupus vulgaris cases [3]. But with improved techniques using multiple media, and the use of Kirchner’s liquid medium for storage of the tissue, the culture positivity will be better. In a recent report from Chennai, the organism was isolated in 55% of cases [6]. The clinicohistologic correlation can be seen in 64% to 80.6% of cases of cutaneous tuberculosis in children [3,13]. The histopathologic correlation is found in 47% to 65.7% of cases of scrofuloderma and 73% to 80% of cases of lupus vulgaris [3,13]. The development of polymerase chain reaction (PCR) to identify the infectious agents has increased considerably the sensitivity of the diagnosis of cutaneous tuberculosis, especially in paucibacillary cases. The combination of hybridization with PCR will further increase the sensitivity and specificity of PCR [39]. A therapeutic trial of antituberculous drugs may be a useful diagnostic tool in developing countries like India. A four-drug regimen (HRZE) is usually given over a period of 6 weeks. Considerable response at the end of 6 weeks would appear to prove the diagnosis of cutaneous tuberculosis [40]. Patients who have not responded by this time are unlikely to do so with further treatment and their diagnosis should be reviewed [41].
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Treatment Cutaneous tuberculosis can be treated with the standard regime used for pulmonary tuberculosis. It consists of the initial 2 months intensive phase with four drugs (rifampicin [8–12 mg/kg], isoniazid [INH] [4–6 mg/kg], pyrazinamide [20–30 mg/kg], and ethambutol [15–20 mg/kg]), followed by 4 months of continuation therapy with two drugs (rifampicin and INH) (2 HRZE/4HR). Some investigators do not use ethambutol in children younger than 5 years because of ocular toxicity, but it can be used with proper monitoring. Patients with extensive skin involvement and the underlying systemic disease may need a longer period of treatment. Currently, the treatment of cutaneous tuberculosis is by the directly observed treatment, short course strategy, implemented by the World Health Organization. This program has been fully adopted by the revised national tuberculosis control program of the Government of India. According to these guidelines, cutaneous tuberculosis is classified as category III, which is treated with three drugs, rifampicin, INH, and pyrazinamide, given thrice weekly for the first 2 months, followed by two drugs, rifampicin and INH, for the following 4 months. When the lesions are extensive, or when more than one group of lymph nodes are involved in scrofuloderma, then the category I regime can be given (2 HRZE/4HR). Summary Cutaneous tuberculosis in children is a major health problem in India. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis. However, the trend in the pattern of cutaneous tuberculosis is changing, as the tuberculid, lichen scrofulosorum, has become more common in recent years. Overall, the clinical patterns are comparable with adults. However, children can have widespread and severe involvement because many unusual and uncommon patterns are known to occur in children. Underlying systemic involvement is more common in children, compared with adults. References [1] WHO. Global tuberculosis control-surveillance, planning, financing. Geneva (Switzerland): World Health Organization; 2006.
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