Cutaneous tuberculosis: Epidemiology, pathogenesis, clinical features and investigations

CTB and immunosuppression

Frequent association of TB with immunosuppressed states such as HIV is well known. India accounted for 71 000 incident HIV-TB co-infected patients in 2019.³ A retrospective study at a tertiary care hospital in northern India showed HIV co-occurrence in 9.1% of all CTB cases. The overall incidence of CTB was 0.7% (131 of 18 720 outpatients).¹⁵ Among 40 cases of CTB, HIV co-occurrence was observed in 2 (5% of CTB) cases.¹⁷ Drug-induced immunosuppression, use of TNF α inhibitors and systemic illness such as leukaemia may allow reactivation of latent TB.

Clinical features of CTB

CTB has varied clinical presentations and patterns, which are defined by the host immunity/hypersensitivity response. In India, limbs are the more common sites for CTB, whereas in the western world, the neck, face, and trunk are common sites.³⁰

Various types of CTB

True CTB and tuberculids. True CTB is where the organism directly affects the skin and can be isolated by various diagnostic methods while tuberculids are a result of hypersensitivity reactions to a distant focus.

Multibacillary and paucibacillary CTB. The multibacillary form is where the TB organism can be seen in microscopy or easily isolated and identified by various techniques. The paucibacillary form is one where isolation of the organism is difficult or not plausible.

Classification by route of infection. Tappeiner and Wolff proposed the most widely accepted CTB classification system, which is based on the mechanism of propagation— exogenous versus endogenous dissemination.³¹

Primary inoculation tuberculosis (PIT) or tuberculous chancre or primary tuberculosis complex

PIT occurs due to inoculation of the TB bacilli on the traumatic sites, e.g, needle prick,³² ear piercing, etc. It is seen often in areas with low vaccination coverage, especially in children.³³ After an incubation period, usually of a few weeks, there is an initial erythematous papule or an erythematous indurated plaque. Gradually, these lesions enlarge and may present either as a cold abscess or ulcerate (Fig. 1). It may sometimes be painful, with or without constitutional symptoms of fever and body ache. Local progression may lead to multiple surrounding lesions. PIT may occasionally evolve into lupus vulgaris or tuberculosis verrucosa cutis.³⁴ Haematogenous spread may lead to distant lesions or systemic involvement.³⁵ It can be divided into two types: primary and post-primary.³⁶

Close

FIG 1.

Tubercular abscess

Export to PPT

Primary occurs in individuals without prior exposure to the TB bacilli. This commonly tends to be ulcerated, inflammatory with regional lymphadenopathy.

Post-primary occurs in individuals already sensitized to the infection. Lesions are warty, less inflammatory and spontaneous regression may occur over months or years.³⁶

Lupus vulgaris

It is one of the common paucibacillary types of CTB, classically presenting as a single or multiple erythematous infiltrated plaques with an advancing active edge and a regressing end with scarring. It usually follows a slow, painless, indolent course and may be covered with scale or crust. Size may vary from as small as a few millimetres to giant lesions. In smaller lesions and in rapidly evolving lesions, scarring may not be evident. It may follow direct inoculation, contiguous spread, haematogenous or lymphatic spread. Lupus vulgaris following ear piercing,³⁷ and after friction of repeated bindi use has been reported.³⁴ Although any site can be involved, the most commonly reported are extremities, buttocks and face (Figs. 2 and 3).³⁷

Close

FIG 2.

Lupus vulgaris. Left hand showing erythematous indurated annular plaque with erosions and scaling on the periphery of the lesion.

Export to PPT

Close

FIG 3.

Lupus vulgaris. Left pinna shows ill-defined erythema and induration with central ulceration and crusting.

Export to PPT

The various variants described are hypertrophic, rapidly progressing facial granuloma,³⁸ ulcerative, sporotrichoid³⁹ mycetoma-like, mimicking squamous cell carcinoma (SCC), keloidal, sarcoidosis⁴⁰ and gangrenous. Differential diagnoses include subcutaneous fungal infections, SCC and atypical mycobacterial infections, and it can be complicated by scarring, secondary infection, destruction of underlying bone and cartilage,⁴¹ contracture if present at joints, dissemination to other sites, and SCC.⁴²

Scrofuloderma (tuberculosis colliquative cutis)

Scrofuloderma is the most common and multibacillary type of CTB, presenting as cold abscesses, ulcerations or growth secondary to direct contiguous spread from underlying tissue. The underlying tissue could be a lymph node, bone, joint, muscle, tendons, epididymis, etc. Involvement of cervical lymph node is the most common⁴³ and scrofula is a term used for cervical TB lymphadenopathy.⁴⁴ The lesion starts as a subcutaneous nodule or abscess, which ruptures to form a fistula or ulcerates (Fig. 4). The ulcers have an undermined edge and a base covered with granulation tissue. Multiple ulcers and matting of lymph nodes can be seen. Surrounding the lesion, scars of old healed lesions or retractions may be seen. Systemic symptoms such as fever, weight loss, and cough may be present. Lupus vulgaris may develop adjacent to the site of scrofuloderma.³³

Close

FIG 4.

Scrofuloderma: Cervical lymphadenopathy with draining sinuses

Export to PPT

Scrofuloderma can occur due to M. bovis and is often the result of the consumption of unpasteurized milk.⁴⁵ It has been reported that fine needle aspiration cytology resulted in CTB in a female with abdominal lymph nodal tuberculosis and HIV infection.⁴⁶ Differentials include atypical myco-bacterial infection, malignancies, osteomyelitis, mycetoma,⁴⁷ hidradenitis suppurativa and histiocytosis. Scarring, secondary infection, dissemination, and chronic discharging sinus may complicate the lesion.

Tuberculosis verrucose cutis (TBVC, warty tuberculosis, Prosector’s wart, butcher’s wart)

TBVC, as the name suggests, is a verrucous hypertrophic variant usually found on the dorsum of the hand, fingers and lower limbs. The forehead is an uncommon site.³⁰ It is commonly seen in children, butchers or others with occupational exposure.⁴⁵ Walking barefoot in contaminated soil is also a risk factor. It starts as a papule, leading to the classical presentation of a single skin coloured erythematous plaque with epidermal hypertrophy and verrucous changes. The individuals presenting with TBVC have moderate to good immunity against the TB bacilli.³³ It is a paucibacillary variant with good response to treatment.

TBVC has to be differentiated from verrucous haemangioma, subcutaneous fungal infection, and verruca. The lesions may be complicated by secondary infection, post-treatment scarring, lymphoedema, and SCC.⁴⁸

Tubercular gumma/Gummatous TB

Gummatous TB usually occurs in immunosuppressed and malnourished individuals. Multiple lesions occur due to haematogenous dissemination from underlying foci of infection. The lesions start as erythematous nodules, which suppurate and later ulcerate. It is a multibacillary form and needs evaluation for the systemic foci. Constitutional symptoms are often present, and the lesions heal with scarring. Other causes of panniculitis, syphilitic gumma, atypical mycobacterial infection, and metastatic nodules have to be considered in the differential diagnosis.

Orificial tuberculosis

Orificial tuberculosis is a result of auto-inoculation of skin or mucosa from visceral sites, such as the lungs, gastrointestinal tract or genitourinary tract, and is seen in patients with low cellular immunity or the elderly.⁴⁹ Common presentations include painful ulcerated lesions surrounding the oral or anal regions. Sometimes, the lesions can be hypertrophic or verrucous.⁴⁹ The prognosis is poor, in part due to severe underlying systemic involvement and early initiation of treatment is essential. It is important to rule out certain conditions, such as SCC, herpes simplex, atypical mycobacterial infection, wart, syphilis, lymphogranuloma venereum and pyoderma gangrenosum.

Miliary TB

This is a rare form of CTB, found predominantly in immuno-compromised individuals like those infected with HIV and spreads through the haematogenous route. The lesions include multiple erythematous papules or plaques, which may later form crusted lesions or ulcerate. Miliary TB presenting as disseminated pustules in a chronic kidney disease patient has been reported.⁵⁰ TB cellulitis and acute miliary TB may appear similarly.⁴⁵ The lesions heal with hypochromic scarring,⁵¹ and it is important to rule out other conditions like systemic fungal infections, pityriasis lichenoides et varioliformis acuta (PLEVA), vasculitis, etc.

TB and mucocutaneous involvement

CTB affecting the face, perianal region and the genitalia can have mucosal involvement along with cutaneous lesions. Olteanu et al. reported TB affecting skin, larynx and lungs simultaneously.^19,52 On the areas surrounding the eye, it can present as dacroadenitis, abscesses, chronic blepharitis and recurrent chalazion.^22,53 Lupus vulgaris affecting the nasal septum, leading to nasal septal perforation has been reported.³⁸

CTB of external genitalia

CTB of external genitalia is rare and needs special mention as it is often missed in the differential diagnosis.

Penile TB. TB may involve the glans penis, penile skin or the coronal sulcus. The presentation may be as a chronic nodulo-ulcerative or papular-nodular lesion, scrofulous gumma and phagedenic infection with destruction of the penis.⁵⁴ The lesions may be single or multiple and with or without lymphadenopathy. Penile swelling and erectile dysfunction may be unusual presentations.⁵⁵ The pathogenesis and modes of transmission are similar except for the addition of possible sexual transmission from the affected partner. Male genitalia is also a site of papulonecrotic tuberculids, which present as asymptomatic, skin coloured or red papules on the glans and penile shaft, which may ulcerate and heal after a few weeks with varioliform scarring.⁵⁶ Apart from ulcerations due to various sexually transmitted infections other differentials could be malignancies and traumatic lesions.

Female genitalia. Female external genitalia may be involved either secondary to upper genital tract TB, haematogenous or lymphatic spread from distant foci or rarely primary inoculation TB of the vulva. Vulval TB is found in about 0.2% of the cases of genital tract TB. Common presentation is as small, shallow ulcers and multiple sinus tracts or rarely as elephantiasis of the vulva or hypertrophic vulval tuberculosis⁵⁷ while other presentations include ulcers of the cervix.⁵⁵

CTB in children

The clinical presentation of CTB differs in children from adults. In contrast to lupus vulgaris in adults, scrofuloderma is the commonest clinical type in children, reported in 36.9%–53.3% of the cases.^58,20 This has been attributed to the intake of unpasteurized milk that can lead to infection of cervical lymph nodes by M. bovis. The spine is another important focus for scrofuloderma. Lupus vulgaris is the second most common form of CTB in children.⁵⁸ However, one series found it to be the most frequent type.³⁰ In contrast to adults where lupus vulgaris occurs on the head and neck, children usually develop it on the buttocks and lower limbs due to the common habit of walking barefoot, playing without clothes and defaecating in the open.²⁰ Lichen scrofulosorum (LS) is increasingly being reported in children in recent years and is the most common tuberculid. In another series, 84% of the 39 LS patients were children <15 years of age. It is associated with systemic focus of TB in 67.6% of the children, most frequently lymph nodes, bones and lungs. In a clinicoepidemiological study of LS from India, 70.5% were children.⁵⁹

Unusual morphologies of CTB are also more frequently observed in children. Sporotrichoid forms of scrofuloderma and lupus vulgaris have been described in children. Multiple forms of CTB can coexist, and CTB in children tends to be more disseminated and extensive compared to adults. Unvaccinated children were documented to have disseminated disease, while the vaccinated group did not develop disseminated disease.⁵⁸ However, the protection offered by the BCG vaccine has been debated in other studies.⁶⁰ Systemic involvement is more likely in children than adults due to the immaturity of their immune system. It varies in different studies from 12.7% to 53.4% and is most commonly detected in lymph nodes, lungs and abdomen.^20,4 There is no definite correlation of HIV disease with CTB in children.

Tuberculids

They are considered hypersensitivity reactions to tubercular bacilli. Ideally, tuberculids show granulomas on histopathology, the tubercular bacteria are not isolated from them, lesions heal with antitubercular therapy (ATT), and there must be an active or latent extracutaneous tubercular foci and tuberculin skin test with strong positivity or a positive interferon-gamma release assay.⁶¹

PNT, LS and erythema induratum are commonly described tuberculids. As there are reports of bacilli being identified in PNT and erythema induratum, classifying them as true tuberculids is debatable.⁶²

PNT. It mainly affects children and young adults with moderate to high immunity. The immune response initiated against the distant tubercular foci leads to recurrent crops of papules and plaques with central necrosis and ulceration. Any cutaneous site can be involved, including the genitalia (Fig. 5). The lesions have a predilection for extremities, with the extensor aspect being commonly involved. In 30%–40% of cases, a primary extracutaneous tuberculous focus is detected, and lymph nodes are the most common location.⁶³ Differentials include systemic fungal infections, PLEVA, Sweet’s syndrome, etc.

Close

FIG 5.

Papulonecrotic tuberculid: Glans penis showing circumferential induration and ulceration.

Export to PPT

LS. It presents as multiple, grouped, tiny skin coloured to erythematous perifollicular papules, sometimes associated with scaling or crusting. These papules coalesce to form plaques. Trunk involvement is common, and lesions may be asymptomatic. The disease often affects children and young adults.³³ LS has been described after BCG vaccination and M. avium infection.⁶⁴ LS confined to the vulva, associated with tubercular lymph-adenitis, has been reported.⁶⁵ History and examination for distant tubercular foci is mandatory and the disease responds well to ATT. Spontaneous healing can also occur in some cases.³³ Differential diagnoses include keratosis pilaris, lichen nitidus, pityriasis rubra pilaris (PRP), follicular psoriasis, and lichen spinolosus.

Erythema induratum. Nodular panniculitis presenting as erythematous tender nodules or plaques on upper and lower limbs is called erythema induratum. It may be multifactorial and has been considered as one of the hypersensitivity reaction patterns to distant foci of TB. ATT-associated improvement in erythema induratum in different series has been reported to be 69%–86%.⁶⁶

Lewandowsky’s rosaceiform eruptions (LMDF). It is a chronic granulomatous entity which presents as erythematous to skin-coloured papules involving the face, including the eyelids and ear. The lesions are resistant to treatment and leave behind scarring. Conlledo et al. isolated TB bacilli in LMDF on the face in 2 patients. This opens a new window for considering LMDF as a form of CTB.⁶¹

Rare presentations of CTB

Occurrence of more than one type of CTB. Multifocal TB is characterized by the presence of large TB areas in the same or different, adjacent or distant organs.⁶⁷ It is also defined as the presence of lesions affecting at least 2 extrapulmonary sites, with or without pulmonary involvement.⁶⁸ Although each clinical form of TB has a unique evolution, the co-existence of more than one form of CTB has been described in the literature. Lupus vulgaris at multiple sites with cold abscess in a young immuno-competent female⁶⁹ and 2 cases of lupus vulgaris and TBVC in the same patient at two different sites have been reported.⁷⁰ Tuberculids and classical CTB can co-exist in the same individuals. There are reports of LS with lupus vulgaris.⁷¹

CTB as complication of BCG vaccine. Bacillus CalmetteGuérin vaccination is known to be associated with local reactions, abscess formation and ulceration. However, scrofuloderma, lupus vulgaris, tuberculids, and, rarely, disseminated infections have also been reported at the site of inoculation.^45,33

Other unusual presentations reported include recurrent CTB resembling cellulitis in a child with a ventriculoperitoneal shunt (VPS),⁷² TB presenting as mastitis⁷³ and CTB presenting as rapidly progressing facial granuloma.³⁸

Investigations and evaluation of patients with CTB

Diagnosis of CTB requires the correlation of clinical findings with the results of investigations. The sensitivity of conventional diagnostic methods, which include smear for acid-fast bacilli (AFB), histopathology, culture and serology, is low because most of the lesions of CTB are paucibacillary. Molecular techniques have also been recently used for diagnosis. Investigations can be grouped as basic tests and specific investigations.

Basic investigations

It is important to routinely screen the patients for HIV status apart from tests like liver function, renal function, blood counts and blood sugar levels in each patient.

Mantoux test

The tuberculin skin test (TST) identifies people sensitized to M. tuberculosis. The Mantoux test indicates the degree of hypersensitivity to tuberculin and has a poor positive predictive value for current active TB.⁷⁴

The sensitivity of the Mantoux test is variable, ranging from 59% to 96% (Table 3).^14,75,76 Overall, it has a low accuracy in identifying patients with CTB. This could be due to a high level of infection with TB and environmental mycobacteria in the community, the presence of delayed-type hypersensitivity to tuberculin in people without CTB, and, on the other hand, the absence of a response in people with active TB.⁷⁶

Tuberculous chancre, miliary tuberculosis and tuberculosis orificialis (the latter mainly by association with AIDS) commonly show negative results. Lupus vulgaris, TVC and LS are the forms that, more often, present strongly reactive tests. Therefore, the other forms are those with more variable results for TST. A negative Mantoux test was observed among patients with multifocal scrofuloderma.^14,75 A negative Mantoux test could also be seen among some lupus vulgaris patients due to primary inoculation or HIV positivity.⁷⁶ Cutaneous anergy, inability to react to skin tests because of a weakened immune system could give rise to a false negative Mantoux test and can indicate an immunosuppressed state.⁷⁷

The increase in the TST cut-off value did not result in increased accuracy of diagnosis (chance to detect cases), because while there was an increase in sensitivity, there was also a decline in specificity. In other words, the higher the TST value, the greater the chance the subject has TB, but the lower the utility in screening the population, because many positive individuals will not be missed.

Mantoux test can be valuable in the assessment of a child with suspected TB, but the interpretation of the result is often difficult, with different induration sizes used to indicate a positive reaction. The positive predictive value of a positive reaction is very high in among children.⁷⁷

Direct demonstration of acid-fast bacilli

Ziehl–Neelsen (ZN) staining is used for the direct demonstration of AFB. In contrast to sputum smear, direct demonstration of M. tuberculosis in CTB has low sensitivity (0%–13.8%), because of the practical difficulty in making a smear from a CTB lesion and the fact that most of the CTB lesions are paucibacillary.^78–81 Wet or exudative lesions of scrofuloderma, TB orificialis, or metastatic TB abscess have a higher bacterial load, hence are more likely to show AFB. Fine needle aspiration cytology (FNAC) specimens can be used to obtain a sample for ZN staining from lesions of CTB. Although ZN staining is widely used, Auramine/Rhodamine dye with fluorescence microscopy is more sensitive for the detection of M. tuberculosis.

Histopathology

CTB is histopathologically characterized by a granulomatous reaction consisting of an accumulation of epithelioid histiocytes with Langhans giant cells with varying central caseation necrosis and a surrounding rim of lymphocytes and monocytes. The histopathological features vary according to different clinical types due to differences in the ability of the host to organize the granulomatous process (Figs 6–8). Histopathological hallmark of granulomatous inflammation was present in 65.7%–100% of CTB patients in various case series.^12,14,20,75 A recent study showed histo-pathology consistent with clinically diagnosed CTB in 75.51% of cases.⁸² ZN stain is commonly used to demonstrate mycobacteria in histopathology, but immunohistochemical stains have been found to be more sensitive.

There are three broad types of histopathological appearance of CTB:⁸³

1. Well-formed granulomas with absence of caseous necrosis

Lupus vulgaris: Epidermis may be atrophic or hyper-trophic, with acanthosis, papillomatosis and even pseudo-epitheliomatous hyperplasia. Well-formed tuberculous granulomas are present with Langhans giant cells in the reticular dermis. There is a dense lymphocytic infiltrate, and AFB are rarely present (Fig. 6).

Close

FIG 6.

Lupus vulgaris shows pseudoepitheliomatous hyperplasia and granulomatous infiltrate in the dermis (haematoxylin and eosin, 400×)

Export to PPT

LS: Epithelioid granulomas are surrounded by lymphocytes and located in periadnexal papillary dermis. Giant cells, caseous necrosis and AFB are not found.

2. Granulomas with caseous necrosis

TB verrucosa cutis: Epidermal changes like hyper-keratosis, acanthosis, and papillomatosis are prominent. Tuberculous granulomas with caseous necrosis are seen in the dermis, and AFB can be found.

Acute miliary TB: A non-specific inflammatory infiltrate composed of lymphocytes and plasma cells is found. The presence of bacilli depends on the severity.

TB orificialis: Tuberculoid granulomas with caseous necrosis are observed in the deep dermis, with a central superficial ulcer.

PNT: Dermal necrosis, accompanied by granulomatous infiltrate, with leukocytoclastic vasculitis (Fig. 8).

Close

FIG 7.

Photomicrograph of scrofuloderma showing loss of epidermis along with dense granulomatous inflammatory mixed cell infiltrate in the dermis (haematoxylin and eosin, 400×)

Export to PPT

Close

FIG 8.

Photomicrograph of papulonecrotic tuberculid showing scale crust and atrophic epidermis overlying an area of focal necrosis in upper dermis (haematoxylin and eosin, 400×)

Export to PPT

3. Poorly formed granulomas with intense caseous necrosis

Scrofuloderma: Extensive central necrosis with abscess formation. Granulomas can be seen at the periphery of the lesion. AFB can be observed (Fig. 7).

Metastatic abscesses and gumma: Extensive caseous necrosis with central ulceration covered by a rim of giant cells and macrophages. AFB are frequently detected.

Culture (LJ media and automated liquid culture systems) Mycobacterial culture remains the gold standard in the diagnosis of CTB. Culture can also distinguish specific types of mycobacteria and antibiotic susceptibility. However, culture from skin biopsy material from cases of CTB, although highly specific, shows low yield, with a range of 0.0%–53.12% for LJ medium.^78,79

A series found positive cultures in 55% patients, the positivity was 57% for lupus vulgaris, 55% for TB verrucosa cutis, and 50% for scrofuloderma. The relatively high culture rate of mycobacteria was due to the use of multiple media (LJ slope, LJ with pyruvate and 7H11 agar) for culture and the use of Kirchner’s liquid medium for preserving the biopsy material till processing.¹²

In an Indian study on 35 untreated patients of CTB, the BACTEC system demonstrated growth of bacilli in 62.8% of samples in 17.3 days, in contrast to conventional LJ medium, which showed positivity in 25.7% of samples in a mean period of 31.5 days.⁸⁴

Molecular tests

Real-time PCR (RT-PCR). The polymerase chain reaction (PCR) has been used in a few studies for the detection of M. tuberculosis. It has been evaluated as a tool in the diagnosis of various forms of CTB, including atypical mycobacteria, but showed variable sensitivity, ranging from 60% to 70%, higher among immunocompromised CTB patients and mostly negative among patients with tuberculids.^78–80 In a study from Mexico on CTB patients, PCR showed a sensitivity of 74%, specificity of 91%, positive predictive value of 94%, and negative predictive value of 64%.⁸⁰

Recent Indian studies have shown much lower sensitivity, although the specificity remained high.^76,85 The sensitivity decreases if clinicopathological correlation is kept as the gold standard rather than culture.

Nucleic acid amplification test (NAAT). CB-NAAT is a cartridge-based, automated diagnostic test that can identify M. tuberculosis DNA and resistance to rifampicin (RIF) by NAAT.

In December 2010, the WHO endorsed the Xpert MTB/RIF for use in TB-endemic countries. The determination of drug susceptibility is important because M. tuberculosis is becoming increasingly resistant to isoniazid and rifampicin, two of the major anti-tuberculosis drugs.

Various studies have shown the sensitivity of CBNAAT to be from 72% to 77% in pulmonary TB.⁸⁶ CBNAAT testing correctly identified 97.6% of rifampicin-resistant mycobacteria and 98.1% of rifampicin-sensitive mycobacteria in PTB patients.⁸⁶ CB-NAAT positivity is much lower (8.7%) in skin tissue samples from CTB patients.⁸²

Serology

Interferon-γ release assays (IGRA). These are T-cell-based blood tests that measure the host response to M. tuberculosis by utilising antigens that are much more specific for M. tuberculosis than tuberculin. IGRAs are more specific than the Mantoux test in the diagnosis of latent M. tuberculosis infection, although the sensitivity is the same as that of the Mantoux test. The two commercially available IGRAs, QuantiFERON®TB Gold InTube test (QFTGIT) and TSPOT®. TB test (TSpot), both employ early secretory protein 6 and culture filtrate protein 10. These antigens are absent in most nontuberculous mycobacteria and all strains of BCG, making these tests useful in individuals who have received BCG vaccination. The QFTGIT assay uses an enzyme-linked immunosorbent assay (ELISA) to measure the concentration of IFN-γ in the plasma supernatant following incubation of blood with the antigens and both negative and positive controls. The T-Spot assay measures the number of IFN-γ producing T cells after overnight incubation in tissue culture plates.

However, the interferon-gamma release assay is not approved as per the National Tuberculosis Elimination Programme.

Serological tests and their role

Serological TB tests are rapid, technically simple, and do not require extensive training. In addition, most of these tests are point-of-care and available at peripheral health facilities where microscopy services are not available. Most of them are based on the principle of ELISA, but some of them are rapid tests. There are few commercially available kits for EPTB. At present, no international guidelines recommend their use, and in fact, international standards for TB care discourage their use in routine practice. Analysis from systematic reviews on the diagnostic accuracy of serological tests indicates that tests are inaccurate, imprecise and not cost-effective for both PTB and EPTB.⁸⁷

Radiological investigations

Different imaging modalities like chest X-ray and ultra-sound abdomen are used to look for systemic involvement and to rule out an extracutaneous focus of TB. Radiological investigations in 107 patients of CTB revealed PTB in 12 patients, TB spine in 1 patient and tuberculoma of the brain in 1 patient.⁷⁴ In a retrospective case review of 216 cases of CTB, extracutaneous focus was seen in lungs (12%), bones (11%), lymph nodes (8%), soft tissue abscess in 3% and disseminated disease in 1%.⁸⁸ Overall, extra-cutaneous involvement was seen in 20%–53% of CTB patients.^{14,18,20,58,60,85} Lymph nodes (29%–64%) and lungs (12%–50%) were most commonly involved.

Dermoscopy. There is limited data regarding dermoscopic features in CTB. In lupus vulgaris, common observations are yellowish-white globules, white structureless areas, white scales and pinkish-red background. Telangiectasias in the form of long linear, branching and short linear vessels are common.⁸⁹ TBVC shows a yellowish to reddish background with papillated surface, dirty white thick scales and yellowish brown areas. Irregularly dilated vessels within the individual papillae with yellow-orange globular and structureless areas were also seen.⁹⁰

Systemic evaluation in CTB

The extent of systemic evaluation depends upon clinical type, host factors and other clinical features. Apart from chest X-ray, other tests are guided by the site of involvement, symptoms and host-related risk factors. X-ray for the lesions located on extremities, joints, and spine may show underlying bone involvement. FNAC from a cold abscess, surrounding lymph nodes, is fruitful in isolating tubercular bacilli. The patient should also be referred to the appropriate specialty in case of extra cutaneous involvement for proper evaluation and management.