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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 202-211

Pediatric cutaneous tuberculosis: Indian scenario


1 Consultant Dermatologist, Shalby Multi speciality Hospital, Mohali, Punjab, India
2 Senior Resident, Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Dr. Bhushan Kumar
Former Professor & Head, Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, #81, Sector 16A, Chandigarh - 160 015
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_63_18

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  Abstract 


Burden of tuberculosis still persists in developing countries despite major advances in its treatment strategies. Cutaneous tuberculosis which is a form of extra-pulmonary tuberculosis is seen in a small but significant subset of patients visiting dermatology outpatient services. Cutaneous tuberculosis is characterized by a spectrum of multiple distinct clinical and histopathology presentations. A significant proportion of patients with cutaneous tuberculosis are seen in paediatric age group. Clinical features in children remain mostly the same as that in adults with cutaneous tuberculosis. However, systemic and lymph node involvement and incidence of disseminated disease is observed more commonly in paediatric age group . Awareness among clinicians of the clinical manifestations of cutaneous tuberculosis is of paramount importance for early diagnosis and management of cases with paediatric cutaneous tuberculosis. This would significantly prevent morbidity and complications of the disease . This review aims to discuss the epidemiology, clinical and histopathological features, diagnosis, differential diagnosis and treatment options in children with tuberculosis, especially in the Indian context.

Keywords: Cutaneous tuberculosis; lupus vulgaris; paediatric cutaneous tuberculosis; scrofuloderma; tubercular


How to cite this article:
Kumar B, Kumar S. Pediatric cutaneous tuberculosis: Indian scenario. Indian J Paediatr Dermatol 2018;19:202-11

How to cite this URL:
Kumar B, Kumar S. Pediatric cutaneous tuberculosis: Indian scenario. Indian J Paediatr Dermatol [serial online] 2018 [cited 2018 Nov 17];19:202-11. Available from: http://www.ijpd.in/text.asp?2018/19/3/202/235496




  Introduction Top


Tuberculosis (TB) is known as a disease of poverty. The burden of TB, especially in developing countries like India still remains a daunting challenge for the global and national health programs. According to the WHO Global TB report 2017, the estimated incidence of TB in India in 2015 was around 2.8 million (27%) out of an estimated global incidence of 10.4 million. In India, the annual incidence of TB in pediatric age group was 0.26 million accounting for 8.9% of overall incidence.[1] The persistence of TB as a global health problem can be attributed to socioeconomic factors such as overcrowding, poor living conditions, poor nutrition, immigration as well as medical factors such as surge in HIV-positive patients and infections with multidrug-resistant strains. Delay in diagnosis and proper treatment of TB patients is a major concern in a country like India. TB was declared as a global emergency in 1993 by WHO, but unfortunately apart from the emergence of drug-resistant strains, nothing much has changed.[2]

Around 18% of newly detected TB cases in India (2015) were extrapulmonary according to WHO data. Cutaneous TB, a form of extrapulmonary TB, accounts for around 0.9% of patients attending dermatology outpatients.[3] Cutaneous TB has a spectrum of multiple yet distinct clinical presentations both in adults and children. Children constitute a significant proportion of overall cutaneous TB cases and present mostly with similar clinical features as that of adult cutaneous TB. Involvement of lymph node and systemic organs along with disseminated presentation is more common in pediatric patients.[3],[4],[5],[6] Thus, early diagnosis and treatment are imperative to avoid significant morbidity and complications in children. The objective of this review is to discuss clinical features, diagnosis, and treatment options in cutaneous TB among infants and children in the Indian context.


  History Top
[7]

TB has been a known entity to humans since ancient times. The tomb portraits of ancient Egypt (3400 BC) civilizations exhibit individuals with hunchbacks demonstrating Pott spine deformities which have been confirmed by the examination of mummies from that era.[8] Old Chinese writings from 2700 BC describes people with emaciation and symptoms of fever cough and hemoptysis suggestive of TB.[8] Hammurabi, the renowned monarch philosopher of Babylonians, has also mentioned about TB in his illustrious code of law of ancient Mesopotamia.[8]

Earliest mentions of cutaneous TB has been in gospels and old testaments in which cutaneous disease resembling lupus vulgaris (LV) has been termed Tsara'ath.[7] Term “Lupus” which means 'wolves” in Latin has been used for skin conditions associated with chronic and disfiguring lesions in mediaeval ages.[9] It was in 1887 when William Tilbury Fox first used the term “LV” specifically for cutaneous TB.[9]

Ancient French writers used the term “scrofulous gumma” for scrofuloderma.[10] Ernest Besnier elaborated about scrofulous gumma in 1883 after the earlier writings of Jean Alibert and Delpech.[10] First published case in history recognizing the association of mycobacterial infection with cutaneous lesions was description of his own prosector's wart by Rene Laennec' in 1826.[11]

Detailed elucidation of histopathological features of cutaneous TB was first published by Carl Rokintansky and Rudolf Virchow.[7] Giant cells and epithelioid cells in skin biopsy of LV were first described by Forster in 1855.[9]


  Epidemiology Top


The proportion of childhood cutaneous TB among overall cutaneous TB incidence in previous studies from India was 63/199 (31.7%),[6] 75/402 (18.7%),[5] 68/142 (47.9%),[3] and 103/191 (53.9%).[4] Apart from India, the prevalence of pediatric cutaneous TB reported were 82% in Pakistan,[12] 6% in Tunisia,[13] 24.3% in Ethiopia,[14] and 36.3% in Hong-Kong[15] of the total cases of cutaneous TB. The disparity in case definition of “childhood” ranging from <14 years to <19 years might have contributed to the difference in prevalence among these studies apart from the regional disparity in prevalence.

In substantial majority of the cases, the age group of 10–14 years was predominantly affected. The time delay in definite diagnosis after disease onset ranged from 2 months to 10 years as reported by Ramesh et al.[6] Kumar et al.[5] found that the time delay in seeking treatment was less than a year in 69% of cases while the delay was >3 years in only 9% of cases. Delay in seeking treatment is one of the factors in predisposing patients to the risk of widespread and disseminated disease and its sequelae of deformity and disfigurement.

A considerable number of pediatric patients were found to have one or more household contacts with positive history of TB in all reported studies. The percentage was noted to be 41% by Pandhi et al.,[3] 32% by Vashisht et al.,[4] and 19% by Kumar et al.[5] implying that household contacts were one of the major source of infections to the children with cutaneous TB. As reported by Pandhi et al.,[3] majority of the patients belonged to lower socioeconomic class living in crowded localities.

As compared to adults, children with cutaneous TB have a higher propensity for lymph node and systemic organ involvement.[16] The prevalence of systemic involvement among paediatric cutaneous TB has ranged from 12.7% to 53.2% in Indian studies.[3],[4],[5],[6] Lungs were the most common systemic organ to be involved followed by bones and abdominal organs.[4]


  Classification and Clinical Features Top


Cutaneous TB can be classified on the basis of route of infection[17] and bacterial load[18] as summarized in [Table 1].
Table 1: Various classification systems of cutaneous tuberculosis[17],[18]

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There exists another simple classification of cutaneous TB for easy comprehension as illustrated in [Table 2].[19],[20] In this classification, cutaneous TB is classified as true TB and tuberculids. True TB is further classified as primary or secondary based on the previous sensitization.
Table 2: Simpler classification of cutaneous tuberculosis[19],[20]

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The clinical presentations of various forms of cutaneous TB are described briefly.

Scrofuloderma

Scrofuloderma is the most common form of cutaneous TB among children.[3],[4],[5] The proportion of scrofuloderma was found to be 53.3% by Kumar et al.[5] and 36.9% by Vashisht et al.[4] Scrofuloderma arises due to contiguous spread of an underlying tuberculous focus to the overlying skin. Lymph nodes are the most common underlying foci out of which cervical lymph nodes being the most common group being involved.[4] The habit of drinking unboiled or unpasteurized milk in rural areas may be one of the contributory factors for infection of cervical lymph nodes.[5] Inguinal, axillary, submandibular, epitrochlear, and supratrochlear lymph nodes are among other commonly affected group of lymph nodes.[19],[20]

Systemic TB foci are seen in up to 66% of cutaneous TB cases. Bones, joints, testes, breast, and lacrimal glands are the other underlying foci of infections leading to scrofuloderma. Hepatic and intestinal TB also is the rare source of cutaneous infections.[3]

Clinically, scrofuloderma is characterized by asymptomatic subcutaneous swellings which persist for several months before softening and ulcerating to form discharging sinuses and ulcers. Typically, the ulcers are shallow with undermined and bluish edges [Figure 1]. Scrofuloderma in children may present with multiple and widespread lesions as compared to adult scrofuloderma where the lesions are more localized [Figure 2]. Scrofuloderma heals typically with cribriform, bridging, and puckered scars.[19],[20]
Figure 1: Scrofuloderma (Photograph courtesy: Prof. Archana Singal, UCMS, Delhi)

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Figure 2: Scrofuloderma in sporotrichoid pattern (Photograph courtesy: Prof. Archana Singal, UCMS, Delhi)

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Lupus vulgaris

LV is the most common variant of cutaneous TB in adults, but in pediatric age group, it is the second most common after scrofuloderma.[5],[16] The proportion of LV among all children with cutaneous TB in major studies from India has been given in [Table 3]. Predominantly, LV is observed most commonly affecting lower half of the body in Indian children including lower trunk, thighs, buttocks, legs, and feet [Figure 3].[3],[4],[6] This pattern can be attributed to the widespread habit of spitting and defecating in open areas and the children squatting and playing without proper clothes and footwear, more so in children with lower socioeconomic background.[6],[16] LV is usually known to manifest in previously sensitized individuals. Although the lesions of LV are solitary, multiple and multifocal lesions can be noted in pediatric age group [Figure 4].[19],[20] The typical lesion of LV is characterized by its onset as asymptomatic papule or small plaque which progresses gradually to form a well-demarcated plaque with evidence of activity at one area and simultaneous healing, atrophy, and scarring at other area resulting in a geographic pattern [Figure 5]. The enlarging plaque is formed by coalescing of multiple microgranulomatous papules which on diascopy are seen as soft, reddish-brown, “apple jelly” nodules more easily appreciated in fair skin. The lesions are usually dry but seropurulent discharge, crusting, and secondary bacterial infection can be seen.[19],[20]
Table 3: Major Indian studies on childhood cutaneous tuberculosis

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Figure 3: Lupus vulgaris over buttocks-central zone of scarring and peripheral zone of activity-plaque variant (Photo courtesy: Prof. Archana Singal, UCMS, Delhi)

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Figure 4: Multiple lesions of lupus vulgaris: Keratotic and ulcerative variants (Photo courtesy: Prof. Archana Singal, UCMS, Delhi)

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Figure 5: Plaque variant of lupus vulgaris with central zone of atrophy and scarring with peripheral zone of activity

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Severe scarring may lead to fibrosis, contractures of the joints, and mutilation in children.[19],[20] Oral, genital, and nasal mucosa can also be involved often as an extension of skin involvement. LV localized to genitalia in children, although rare, can lead to severe mutilation and scarring, especially of vulva.[6] Rarely, destruction of ear and nose can also be seen [Figure 6]. Contractures involving knee, elbow, and wrist joints are other disabling sequelae of LV.[3],[6],[16],[21]
Figure 6: Mutilating lupus vulgaris over face (Photo courtesy: Prof. Archana Singal, UCMS, Delhi)

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Morphological variants of LV include classic plaque [Figure 7] or keratotic type [Figure 8], hypertrophic, ulcerative, atrophic, and papulonodular. Keratotic type is most commonly seen whereas ulcerative and atrophic variants are the least common in children.[19],[20]
Figure 7: Lupus vulgaris over knee-plaque variant (Photo courtesy: Prof. Archana Singal, UCMS, Delhi)

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Figure 8: Lupus vulgaris over dorsum of hand-keratotic variant

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Apart from the classical clinical variants, kissing LV, involving the gluteal cleft, and multifocal lesions involving the head-and-neck area, extremities, and mucosae are the unusual clinical variants of LV reported in children. Symmetrical LV involving the knees and ankles possibly due to exogenous inoculation of the organism has been reported. Atypical forms of LV can be seen in children such as deeply destructive papillomatous and sclerotic variants leading to deformities of the limbs. LV with a sporotrichoid pattern due to lymphatic spread has also been described [Figure 9].[4],[5],[19],[20] LV developing at the site of Bacillus Calmette–Guerin (BCG) vaccination and near the opening of scrofuloderma sinus has also been reported.
Figure 9: Lupus vulgaris in sporotrichoid pattern

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Constitutional symptoms are generally absent or very mild and systemic involvement is less commonly seen as compared to scrofuloderma. Regional lymphadenopathy is frequently associated with LV.[4],[5],[19],[20]

Tuberculosis verrucosa cutis

Also known as warty TB, tuberculosis verrucosa cutis (TVC) manifests after exogenous inoculation of tubercule bacilli in previously sensitized individuals with good immunity. The prevalence of TVC predominantly in pediatric group has been <4.5% in studies reported from India.[16] The lower part of the extremities is most commonly involved due to trauma. Lesions of TVC present characteristically as verrucous papules and plaques, with fissures, clefts, and crusting over the surface [Figure 10]. Lesions may extrude pus, and perilesional inflammation and erythema may be seen. Serpiginous outline is seen commonly due to irregular extension of the lesions with involution at the center.[16],[19],[20] Symmetrical lesions of TVC on the extremities have been described.[22] There is absence of constitutional symptoms while lymph nodes may be enlarged.[20]
Figure 10: Tuberculosis verrucosa cutis (Photo courtesy: Prof. Archana Singal, UCMS, Delhi)

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Tuberculous gumma

Tubercular gumma, also known as metastatic abscess, results from disseminated infection by the hematogenous route from a primary focus during periods of lowered resistance. Children with malnutrition, immunosuppression, or lymphomas are more susceptible compared to general population.[20] It is considered to be the severe variant of scrofuloderma by few authors. The typical lesion is characterized as single or multiple soft, dermal, or subcutaneous nodules which soften(s) to form fluctuant nontender abscesses and later breaking down to form ulcers or sinuses with undermined edges. Multiple confluent swellings and sinuses affecting contiguous groups of lymph nodes with finger-like extensions radiating across the neck or chest wall can be seen sometimes. On histopathology, tubercles with caseation necrosis are characteristically seen. Acid-fast bacteria (AFB) are usually easily isolated from the pus.[16],[20]

Tuberculosis cutis orificalis

It is caused by autoinoculation of the organisms in individuals with abdominal or pulmonary TB and is seen rarely in children. Oral cavity is the most commonly involved site followed by the genital or anal mucosa. Shallow, granulomatous, and painful ulcer with undermined bluish edges is the typical presentation.[19]

Acute miliary tuberculosis

Acute miliary TB is the more florid variant of TB due to hematogenous dissemination of Mycobacterium tuberculosis. Cutaneous findings consist of widespread erythematous papules, pustules, or vesicles or nonspecific lesions. Marked constitutional symptoms are common along with internal organ involvement especially the lungs and meninges. Tuberculin skin test is typically negative. Acute inflammatory cells with numerous microabscesses are seen on histopathology. The organisms are usually demonstrated on aspiration smear or histopathology.[19],[20]

Tuberculids

Tuberculids result from a delayed-type hypersensitivity reaction to occult tubercle bacilli in a patient with moderate to high immunity. The diagnostic criteria of tuberculids include tuberculoid granuloma on histopathology, strongly positive Mantoux test, absence of M. Tuberculosis in smear and culture, and resolution of skin lesions with antituberculous therapy (ATT). Classification of tuberculids is discussed in [Table 1]. Erythema nodosum is considered to be a facultative tuberculid as M. Tuberculosis is one of the many causative factors for erythema nodosum. Despite the smear and culture negativity for M. tuberculosis, polymerase chain reaction (PCR) techniques have identified mycobacterial DNA in the lesional tissue of all types of tuberculids.[19],[20]

Lichen scrofulosorum

Lichen scrofulosorum is the most common variant of tuberculids seen in children. The prevalence of lichen scrofulosorum in different Indian studies in children is summarized in [Table 3]. While earlier Indian studies had reported lower frequency of LS, recent reports show higher prevalence.[16] Higher index of suspicion may be responsible for higher prevalence in recent studies. Lichen scrofulosorum is an underdiagnosed and underreported condition as subtle and asymptomatic lesions are either missed or misdiagnosed as other follicular conditions such as lichen nitidus, keratosis pilaris, and pityriasis rubra pilaris. Although M. tuberculosis is commonly associated with lichen scrofulosorum, rare association with Mycobacterium avium Scientific Name Search  intracellulare and Mycobacterium szulgai infections have been reported.[23]

Lichen scrofulosorum typically presents as asymptomatic or mildly symptomatic, pin-head-sized grouped or clustered follicular, and parafollicular papules mostly over the trunk [Figure 11]a and [Figure 11]b or proximal extremities which can be skin colored, erythematous, or lichenoid in color.[20] The papules are characteristically flat-topped although overlying micropustules or crusting can be seen. Extensive psoriasiform lesions have been reported in lichen scrofulosorum.[24] Coexistence with other forms of cutaneous TB such as scrofuloderma, LV, and erythema induratum has been seen.
Figure 11: (a and b) Lichen scrofulosorum- multiple, pinhead-sized grouped, follicular, and parafollicular papules over trunk (Photographs 11a and b courtesy: Prof. Archana Singal, UCMS, Delhi)

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Underlying focus of TB is seen in substantial majority with lymph nodes (cervical, mediastinal or hilar) being the most common involved foci, followed by lung and bone.[4],[20]

Papulonecrotic tuberculid

Papulonecrotic tuberculid (PNT) is a less common form of tuberculid as compared to lichen scrofulosorum. The prevalence of PNT in children was around 4% in as reported by Vashisht et al.[4] while earlier studies reported almost zero prevalence of PNT.[3],[5],[6] The typical lesions are characterized by symptomatic symmetrically distributed firm and dusky-red necrotizing papules over the extremities which heal by varioliform scarring. The acral regions are the common sites of predilection; however, lesions localized to buttocks and face have been described. Association with pulmonary and lymph node TB and phlyctenular conjunctivitis have been described.[16],[19],[20]

Erythema induratum of Bazin

It is the rarest form of tuberculid with no childhood case reported from India till date.[23] It is characterized by subcutaneous nodules over posterior aspect of legs which break down to form an ulcer healing with atrophic scar. Lobular panniculitis with vasculitis is seen on biopsy along with strongly positive Mantoux test. PCR for mycobacterial DNA is positive in more than 50% of cases.[25] Frequent association with pulmonary TB is seen.[26] While erythema induratum and nodular vasculitis has been used interchangeably in the past, it has been found that not all cases are associated with TB. It has been proposed that the term “erythema induratum of Bazin” should be reserved for those cases only which are associated with TB. The term “erythema induratum of Whitefield” had been used in the past and presently nodular vasculitis, for cases not associated with TB.

Sporotrichoid skin tuberculosis

Lymphatic spread of the tubercular infection from a primary entry focus can lead to linear arrangement of the lesions, mostly over the extremities. Such pattern is called sporotrichoid pattern as it resembles the linear lesions of sporotrichosis. Sporotrichoid skin TB has most commonly been reported among children from developing countries.[27],[28] Similar to sporotrichosis, cord-like thickening of the lymphatics may also occur. Regional lymphadenopathy and ulceration can also be seen. Among the variants of cutaneous TB, scrofuloderma and LV lesions often present in sporotrichoid pattern. Retrograde lymphatic spread of the organism from inguinal lymph nodes can lead to inverse sporotrichoid pattern. This refers to occurrence of linear lesions in proximal lower extremities, mostly associated with TBVC and tubercular gumma.[19],[20]

Bacillus Calmette–Guerin and cutaneous tuberculosis

Although BCG seems to have a significant efficacy in prevention of pulmonary, miliary, meningeal and other forms of systemic TB,[29],[30] the role of BCG in prevention of cutaneous TB is not well established. BCG vaccination was found to be effective in prevention of skin TB in the study by Zodpey et al. with an efficacy of 60.9%.[31] No difference in the incidence and clinical presentation of cutaneous TB was found between BCG vaccinated and unvaccinated children in one of the earlier studies.[6] LV, scrofuloderma, tuberculids and erythema nodosum have been reported at the site of BCG vaccination. As compared to typical cutaneous TB, cutaneous TB induced by BCG vaccination develops more quickly and is less severe in presentation and easier to treat.[19]

HIV and cutaneous tuberculosis

Some forms of cutaneous TB, tubercular ulcers, PNT, and miliary forms are more frequent and severe in HIV-positive individuals. In any of the major studies from India, no child with cutaneous TB was found to be HIV positive. Hence, larger studies are required to establish the impact of HIV seropositivity on cutaneous TB in children.[16],[20]


  Diagnosis Top


The diagnosis of cutaneous TB is based on clinical features and laboratory tests. Differential diagnoses usually include atypical mycobacterial infections, deep fungal infections such as chromoblastomycosis and sporotrichosis, sarcoidosis, cutaneous leishmaniasis and leprosy. Major laboratory investigations include direct demonstration of AFB on Ziehl–Neelsen (ZN) stained smears or biopsies, histopathology, isolation by culture or detection by PCR, and Mantoux test. Multiple meta-analysis and WHO studies have confirmed that serological antibody detection tests for TB are of no clinical utility owing to their inaccuracy and inconsistency and have been strongly discouraged for the diagnosis of TB.[32]


  Histopathology Top


Biopsy for histopathology[33] and culture should be taken from the edge of the sinus or ulcer which would show tuberculoid granuloma along with neutrophils, eosinophils, and caseation necrosis. Characteristic tubercular epithelioid cell granulomas with lymphocytes and Langhans type giant cells are the hallmark of cutaneous TB. However, nonspecific changes can be seen in some cases. In addition, the presence of tuberculoid granulomas in other diseases can pose a diagnostic dilemma. Clinicopathological correlation has been observed in 64%–85% of cases of cutaneous TB in children.[3],[4] LV is more often associated with classical tubercular histopathology as compared to scrofuloderma. Histopathology is especially useful for the diagnosis of tuberculids in cases where ZN staining and isolation by culture is not possible.[16]

Cutaneous tuberculosis variants with well-formed granulomas without caseation necrosis

Lupus vulgaris

The typical histopathology of LV shows epithelioid granulomas in the upper dermis with lymphocytes and Langhans giant cells in around 80% of cases. Rarely, foreign body or sarcoidal granuloma can also be seen. Nonspecific changes are seen in around 20% cases.[16] The epidermis is characterized by atrophy or hypertrophy with acanthosis, papillomatosis and sometimes pseudoepitheliomatous hyperplasia. There is dense lymphocytic infiltrate. Fibrosis is seen in areas of scarring. There is a paucity of AFB and detection of bacilli by staining and culture is difficult.[19]

Lichen scrofulosorum

Epithelioid cell granuloma with cuff of lymphocytes surrounding the follicles and sweat ducts, located more superficially in dermis are demonstrated on histopathology.[4],[23] Giant cell, caseous necrosis, and AFB are not seen usually. PCR and culture for tubercle bacilli from lesional skin biopsies are usually negative.[23]

Cutaneous tuberculosis variants with granulomas and caseous necrosis

Tuberculosis verrucosa cutis

The typical histopathology shows hypertrophic changes such as pseudoepitheliomatous hyperplasia, tuberculoid granulomas with caseous necrosis in the mid-dermis, and the presence of acute infiltrate in the upper dermis. AFB are demonstrated rarely.[4],[16]

Acute miliary tuberculosis

Nonspecific inflammatory infiltrate mainly of lymphocytes and plasma cells is seen. Focal caseous necrosis can be seen with formation of microabscesses occasionally. AFB are frequently demonstrated with their number varying according to the severity of the condition.[33]

Tuberculosis cutis orificialis

Tuberculoid granulomas with caseous necrosis is seen in deep dermis around the site of ulceration.[33]

Papulonecrotic tuberculid

Wedge-shaped necrosis along with nonspecific perivascular infiltrate or typical tubercular granulomas surrounding the necrosis are the typical histopathological findings, along with leukocytoclastic vasculitis, and perivascular edema or follicular necrosis with suppuration. AFB is not usually demonstrable in PNT lesion; however, it is not unusual to detect M. tuberculosis DNA by PCR.[16],[34] It has been suggested by Jordaan et al. to use the term “papulonecrotic TB” over “PNT where M. tuberculosis DNA can be confirmed by PCR.[35]

Cutaneous tuberculosis variants with poorly formed granulomas with intense caseous necrosis

Scrofuloderma

Scrofuloderma is characterized by the presence of large central necrosis with the formation of abscess and in most cases, suppuration. Traces of the granuloma and AFB when present are seen at the periphery of the lesion.[33]

Mantoux test

Mantoux test is a simple screening test to detect the presence of tubercular infection. Induration of 10 mm or more is suggestive of infection but does not confirm the presence of active disease.

The sensitivity of Mantoux test for cutaneous TB ranges from 33% to 96% with a cutoff of 10 mm. In the study by Ramam et al.,[36] specificity of Mantoux with a cutoff of 10 mm was found to be 62.5%. The sensitivity of Mantoux test in unvaccinated patients is much higher, close to 97%.[36]

The sensitivity and intensity of Mantoux test varies widely among the different presentations of cutaneous TB. While Mantoux test is usually negative in tuberculous chancre, miliary TB and TB orificialis, strongly reactive Mantoux is seen usually in scrofuloderma, LV, TVC, and the tuberculids.[8]

Exposure to environmental mycobacteria as well as recent BCG vaccination within 1 year can lead to false-positive results. Age <2 months, pregnancy, and immunosuppressed states such as malnutrition, diabetes, and HIV can be associated with false-negative reactions.[33] The rate of Mantoux positivity in major Indian studies on pediatric cutaneous TB has been given in [Table 2]. Vesiculation and ulceration can occur in children after severe Mantoux reaction.[3],[4]

Direct demonstration of acid-fast bacteria

Direct demonstration of AFB in skin biopsy specimens using ZN stain is a confirmatory test for the diagnosis of cutaneous TB. Compared to culture, it is less time-consuming. However, the sensitivity is inferior and observer dependent as compared to culture and molecular-based tests.[16]

Culture

Positive culture is considered to be the gold standard for diagnosis of cutaneous TB as for any other infectious disease. Culture has an additional advantage of being able to test drug susceptibility. Traditional L-J medium has low rates of positivity for cutaneous TB especially in children.[3],[4] Owing to low sensitivity and tedious procedure of traditional culture systems, newer culture methods such as Radiometric BACTEC TB culture system and liquid media are gaining popularity. Middlebrook 7H12 broth medium containing C-14 labeled palmitic acid for radiometric detection of mycobacteria is used in BACTEC culture method.[37] In a study by Aggarwal et al., the sensitivity (62.8% vs. 25.7%) and mean detection time (17.3 days vs. 39.4 days) of BACTEC system fared better as compared to conventional L-J medium. The study also concluded that the combined isolation rate using both media was superior as compared to either medium used separately.[37]

Polymerase chain reaction

PCR is a rapid method with a reasonable sensitivity and specificity to detect cutaneous TB.[25],[38] IS-6110 gene specific for M. tuberculosis complex is the most common target used in PCR.[25],[38] Nonetheless, PCR requires intensive labor and skill and is susceptible to technical errors. Carryover contamination may lead to false-positive results. Degraded target DNA, insufficient extraction of target DNA, and clinical samples-containing PCR inhibitor substances are common causes of false-negative results.[37] PCR is not able to distinguish live from dead bacilli. High cost of this technique and inability to test drug susceptibility are additional disadvantages of PCR.[16]

Therapeutic trial with antituberculous therapy

The rapid clinical response in case of cutaneous TB has led to the concept of therapeutic challenge with ATT as a diagnostic modality in doubtful cases where laboratory results are equivocal.[39],[40] As suggested by Ramam et al., 5 weeks were found to be an adequate duration for a therapeutic trial in suspected cases of cutaneous TB. In the absence of any significant response by 5 weeks, the authors concluded that further treatment was unlikely to be beneficial.[41],[42] In these cases, possibility of MDR-TB or a diagnosis other than cutaneous TB should be considered. However, tuberculids are an exception as they may require more than 5 weeks to respond. Thus, prolonging the therapeutic trial is advised in case of tuberculids before considering alternate diagnosis.[42]

Systemic screening for tuberculous focus

In all children with cutaneous TB, thorough clinical assessment should be performed focusing on lymph nodes, pulmonary, gastrointestinal, nervous system, ocular, and musculoskeletal system. Fine-needle aspiration cytology and culture should be performed from any suspicious lesions. X-ray of the chest and joints, computed tomography scan/magnetic resonance imaging of the brain and spine, ultrasonography of the abdomen and pelvis, sputum and urine for AFB, and mycobacterial culture should be undertaken to rule out tuberculous foci in any of the organ suspected to be involved based on clinical findings.


  Treatment Top


Relaunch of our Revised National TB Control Program (RNTCP) has resulted in better control and management of pulmonary and extrapulmonary TB in India especially after scaling-up of directly observed treatment, short course (DOTS). According to a recent study, scaled up DOTS has been a cost-effective strategy which has been successful in improving the health status of Indian population. There has been recent modification of DOTS by RNTCP in which thrice-weekly regimen in previous guidelines has been replaced by daily regimen in the newer guidelines. In addition, the continuation phase has been modified to include three drugs in newer guidelines instead of two drugs in the previous guidelines.

Cutaneous TB is treated as extrapulmonary TB as per DOTS Category I recommendations. Intensive phase consists of HRZE (isoniazid, rifampicin, pyrazinamide, and ethambutol) given daily for 2 months followed by maintenance phase of 4 months of HRE (isoniazid, rifampicin, and ethambutol) daily. WHO defines MDR-TB as resistance to isoniazid and rifampicin and XDR-TB as resistance to isoniazid, rifampicin along with any fluoroquinolone and one of the 3 second-line injectable drugs (amikacin, capreomycin, and kanamycin). No studies on drug resistance patterns in children have been done till date, although few cases of drug resistance in children have been published. The dosage of first-line and second-line ATT drugs by weight has been given in [Table 4].
Table 4: Antitubercular drugs

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Treatment of MDR-TB requires the use of second-line drugs. The treatment regimen usually consists of five or six drugs which include a fluoroquinolone and an injectable administered for 6 months followed by administration of four oral drugs for the next 18 months. The toxicity of second-line drugs warrants close monitoring especially in children.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Pandhi D, Reddy BS, Chowdhary S, Khurana N. Cutaneous tuberculosis in Indian children: The importance of screening for involvement of internal organs. J Eur Acad Dermatol Venereol 2004;18:546-51.  Back to cited text no. 3
    
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