A rare case of drug resistant tuberculosis lupus vulgaris – a case report

Cutaneous tuberculosis (TB) is an important clinical and diagnostic challenge and accounts for 1.5% of TB that occurs at extrapulmonary sites. It is caused by Mycobacterium tuberculosis, Mycobacterium bovis and, rarely, Bacille Calmette-Guérin (BCG) vaccine. It can present or coexist with other forms of TB, especially pulmonary TB and lymph node TB. It can be acquired either exogenously or endogenously and can mimic the clinicopathological features of various other skin diseases. The underlying systemic or organ TB can be notoriously difficult to detect, resulting in considerable diagnostic challenges and potential delays in diagnosis and institution of treatment (1).

A 15-year-old male presented to the dermatology section with a single raised, non-painful and itchy lesion over the right foot near the base of the small toe for 4 years. There was no history of contact with TB patients, trauma or any known immunocompromised health status. It started as small lesions and increased to the present size >4 years. The patient was seen by dermatologist in 2018 for the same lesion and was started on rifampicin, isoniazid and clarithromycin for 11 months. The patient showed no improvement, and in view of the increasing lesion size, a biopsy was done. Biopsy was suggestive of lupus vulgaris. The patient was started on isoniazid, rifampicin, ethambutol and pyrazinamide but took the medications only for 3 months and was lost to follow-up. The patient had no improvement with this treatment. The size of the lesion increased to the current size, and patient had complaints of occasional bleeding from the lesion. The patient did not have any respiratory complaints. On examination, there was a single verrucous plaque 1 cm × 1.5 cm indurated on the right leg at the base of the right little toe (Figure 1). Routine blood investigations and chest radiograph (Figure 2) were normal. Cartridge-based nucleic acid amplification test (CBNAAT) of the skin biopsy detected MTB, and rifampicin resistance was also identified. Mycobacterium growth inhibitor tube (MGIT) culture report showed no growth after 6 weeks. Ultrasound (USG) abdomen showed a few enlarged lymph nodes with well-preserved morphology noted in the right iliac fossa, the largest measuring 1.5 cm × 1 cm. Skin biopsy histopathology showed prominent hyperkeratotic stratum corneum with epidermal verrucous hyperplasia. Epidermal showed prominent acanthosis, with superficial dermis showing dense chronic inflammatory infiltrate consisting of a large number of lymphocytes (Figure 3). The final diagnosis was lupus vulgaris due to drug resistant TB. The patient was initiated on second-line anti tuberculosis treatment (ATT) kanamycin, high-dose isoniazid, high-dose moxifloxacin, clofazimine, ethionamide, ethambutol and pyrazinamide and showed clinical response at 2 months follow-up (Figure 4). This therapy was in accordance with the shorter regimen for drug-resistant TB prescribed as per then prevailing National tuberculosis elimination program (NTEP) guidelines for programmatic management of drug resistant TB in India, which was just before the availability of bedaquiline under programmatic conditions. The patient received 4 months of kanamycin, high-dose isoniazid, high-dose moxifloxacin, clofazimine, ethionamide, ethambutol and pyrazinamide followed by 5 months of high-dose moxifloxacin, clofazimine, ethambutol and pyrazinamide. The patient showed clinical improvement and was declared treatment-completed at 9 months of the shorter regimen.

Figure 1:

(A, B) Single verrucous plaque indurated on right leg at base of right little toe.

Figure 2:

(Normal chest radiography.

Figure 3:

Skin biopsy histopathology showing prominent hyperkeratotic stratum corneum with epidermal verrucous hyperplasia, papillomatosis and acanthosis. Superficial dermis shows dense chronic inflammatory infiltrate consisting of large number of lymphocytes.

Figure 4:

Skin lesion with response.

Cutaneous TB is an uncommon form of extrapulmonary TB (EPTB) and is often difficult to distinguish and diagnose from other skin lesions. Lupus vulgaris is the most common variety reported from India, followed by TB verrucosa cutis and scrofuloderma. Lupus vulgaris can follow inoculation of organisms into the skin of patients with previous or current TB, but more often, it follows haematogenous or lymphatic dissemination to the skin from underlying and often subclinical TB. Less commonly, it may develop at the site of BCG inoculation (2). The skin lesions are characterised by coalescing papules that form a plaque that has traditionally been described as resembling apple jelly nodules on diascopy (1). Although the head and neck and especially the nose are typically involved, lupus vulgaris may less commonly involve the limbs and feet, gluteal area, trunk and penis (3). Disseminated lesions may also occur. Children used to account for about a quarter of all patients of skin TB in India. Lupus vulgaris is a chronic condition, and it is often characterised by considerable delay in arriving at the correct diagnosis (4). Subsequent scar formation is therefore not uncommon. Squamous cell carcinoma and less commonly basal cell carcinoma, melanoma and lymphoma may complicate long-standing lupus vulgaris (5, 6). Histopathological features include intradermal tuberculoid granulomas with little or no necrosis, mimicking sarcoidosis. Pseudoepitheliomatous hyperplasia of the epidermis, especially in superficial biopsies, may simulate squamous cell carcinoma. Rarely, epidermal atrophy and ulceration may be present. Organisms are usually rare and difficult to find in Ziehl–Neelsen-stained sections (1). Cutaneous TB presents with lesions that gradually keep appearing. The patients also have constitutional symptoms such as weight loss, fever and poor appetite. A clinical diagnosis of cutaneous TB can be made with reasonable confidence in most cases. The diagnosis should be confirmed by a skin biopsy, microbiological culture in broth-based culture medium or molecular techniques such as PCR (7). Barring a few reports, culture has not been an important prerequisite because of poor isolation rates. Treatment regimens are similar to those used for TB in general. If there is no visible clinical and dermatological response after 6 weeks, the patient should be re-evaluated. Regular follow-up and compliance to treatment are essential (1). Drug-resistant infection should be suspected in patients presenting with typical clinical features who fail to respond to first-line drugs. The problem of confirming the diagnosis of cutaneous TB caused by drugresistant TB remains unresolved. Owing to the low bacillary load, particularly in lupus vulgaris, isolation of organisms is difficult and molecular tests for detection of resistance have low sensitivity. Clinico-radio-microbiological confirmation is necessary for diagnosis of drug-resistant TB. Our dermatology group reported a similar case involving lesions on the knee (8). Authors have reported multidrug-resistant lupus vulgaris with Poncet’s disease (9). All cases highlight the difficulty in diagnosis and the need to suspect and test with microbiology tests in all cases, given the ease of availability of CBNAAT (10). In our patient, a timely clinical suspicion helped us in expanding and pursuing a microbiological diagnosis, and a CBNAAT performed along with the culture clinched the accurate microbiological diagnosis.