Tuberculosis (TB) is a major global health problem. According to the World Health Organization,1 one third of the world’s population is thought to be infected with TB. In 2016, there were 10.4 million cases of active TB resulting in 1.3 million deaths. More than 95% of deaths occurred in developing countries. On the other hand, TB has become uncommon in high-income countries, especially among children. With the recent waves of migration, however, old diseases are reappearing and attention is required not to overlook the diagnosis of the atypical forms of TB. We report here the case of an adolescent girl who developed a multifocal form of cutaneous TB in addition to pulmonary involvement.
A 14-year-old girl of Pakistani origin who had been in Italy for 1 year presented to our emergency room because of several painful cutaneous lesions that had appeared 2 months earlier.
One of the lesions was in the first toe of the right foot, one involved the palm of the right hand and was accompanied by moderate swelling of the dorsal surface of the extremity (Fig. 1A, D).
In addition, 2 deep ulcers with sharp margins of approximately 5 mm each were present on the left buttock. Three months earlier, the ulcers had dripped a grayish fluid (Fig. 1C).
The patient did not complain of cough, fever, night sweats or other systemic symptoms. However, she had unintentionally lost 5 kg in the last year. She had no palpable lymphadenopathy.
Complete blood count was not remarkable (hemoglobin 13 g/dL, white blood cell count 7.4 × 103/μL with neutrophils 62%, lymphocytes 26%, C-reactive protein 1.5 mg/dL, erythrocyte sedimentation rate 52 mm/h).
Also, the immunoglobulin pattern, the lymphocyte subpopulation and the complement system were within normal limits. HIV serology was negative.
After admittance for possible bacterial infection, she was treated with piperacillin-tazobactam and clindamycin, with no benefit.
Microbiologic cultures of the material drained from the lesions were negative, as well as repeated blood cultures.
She had been vaccinated against TB in Pakistan, her purified protein derivative tuberculin test resulted in an induration of 25 mm of diameter after 72 hours (15 mm or more is positive in individuals without any risk factors for TB; reactions larger than 15 mm are unlikely to be due to previous Calmette-Guérin bacillus vaccination or exposure to environmental mycobacteria) and the interferon-gamma release assay was positive (specific antigen TB1 1.32 UI/ml, TB2 1.83 UI/ml).2
A Computed Tomography (CT) scan of the chest showed several enlarged lymph nodes associated with areas of parenchymal consolidation.
Samples obtained by bronchoscopy and by gastric lavage were negative for mycobacteria.
Within 1 week, the hand lesion had increased to 4.5 cm and protruded 1.5 cm (Fig. 1B).
Debridement and drainage of the lesion yielded 8.5 ml of white, cloudy fluid that was sent for culture, direct microscopy and polymerase chain reaction (PCR) assay examination. Similar fluid could be obtained from the toe but not from the gluteal lesions.
Acid-fast mycobacteria, which were positive by Ziehl–Neelsen staining, were seen in the pus from the hand and toe. Also the rapid PCR assay and cultures from both sites were positive for Mycobacterium tuberculosis.
Drugs susceptibility testing showed the first-line chemotherapy (rifampicin, isoniazid, pyrazinamide and ethambutol) to be effective. A diagnosis of TB was made and treatment was started. An magnetic resonance imaging of the hand showed destruction of the cortex and periosteum of the fourth metacarpal bone, bone marrow edema and fluid collection in the adjacent soft tissue (Fig. 2). No other radiologic bone lesions were visible.
The girl presented an excellent response to treatment showing resolution of the skin lesions within 2 months; her therapy will last for at least 12 months.
In children TB remains a major health problem worldwide, especially in developing countries.
During the last several years, extrapulmonary tuberculous infections have outnumbered the cases of pulmonary TB.
Cutaneous TB is rare in Western countries. The high incidence of TB reported from in the United Kingdom was mainly localized in an area with many residents coming from the Indian sub-continent.
It mainly affects immunocompromised individuals, either infected with HIV or undergoing immunosuppressive therapies.3,4
Several studies have shown that Calmette-Guérin bacillus vaccination prevents 50% to 80% of severe TB, but it does not appear to prevent skin TB.5
In India childhood skin TB accounts for about 1.5% of all the cases of extrapulmonary TB.6 In Pakistan 82% of all cases of skin TB were reported in children.7
Cutaneous TB can enter the skin through small lesions, or, more frequently, in the presence of active pulmonary TB, the infection reaches the skin and soft tissues via the bloodstream and the lymphatic system. The skin lesions can appear even years or decades after the primary infection.8
Skin TB presents several clinical forms and it can be classified into primary and secondary disease, depending on previous sensitization to the Mycobacterium.
In reports from Pakistan and India, scrofuloderma was the most common form of skin TB, followed by lupus vulgaris, and by the far less frequent TB verrucosa cutis and tuberculids.
Scrofuloderma begins as asymptomatic subcutaneous swellings which often break down to form ulcers or discharging sinuses. Ulcers are usually shallow and undermined with bluish margins. Scrofuloderma may heal spontaneously over a period of years with cerebriform or bridging scars. It usually develops from the contiguous spread of infection from underlying tuberculous focus, most often from the cervical group of lymph nodes, but it can also develop from infection of bones, joints or other sites.
Lupus vulgaris begins as slowly progressing asymptomatic papules and plaques. The enlarging plaque shows an active peripheral margin and central atrophy with scarring.
It can cause severe fibrosis, contractures of the joints and mutilation. Lupus vulgaris may affect also the oral, nasal or genital mucosae as an extension of the skin lesions.8
The spectrum of skin TB in children is comparable with that in adults, but extensive and disseminated involvement with several unusual variants is more common in children. Delay in diagnosis and treatment can cause serious morbidity and disability.
In the case of our patient, TB had most likely spread to the skin and the hand bone via the blood from the initial pulmonary focus. In a pediatric study, skin TB originated most commonly from lung involvement (45% of cases) followed by bone (35%) and lung and bone involvement (15%).8
The diagnosis of cutaneous TB is elusive and must be differentiated from leishmaniosis, leprosy, actinomycosis, tularemia, cat-scratch disease and deep fungal infections. The concomitant presence of TB in other body districts, mainly the lungs, makes the diagnosis more likely. Confirmation of the diagnosis must be obtained by skin test, interferon-gamma release assay, microbiologic examination of bioptic tissue and PCR.9 Although surgical intervention might be useful for isolated lupus vulgaris, TB verrucosa cutis and for some cases of scrofuloderma. Cutaneous TB, after drainage of any abscess, must be treated with a short-course of four-agent chemotherapy (ethambutol, isoniazid, rifampicin and pyrazinamide) given for 8 weeks, followed by a 2-drug regimen (isoniazid and rifampicin) for the next 16 weeks.10
Prophylactic pyridoxine should be added to the regimen to prevent isoniazid-related neuropathy, particularly in breastfed or undernourished children.
It is important to treat the disease as early as possible to prevent relapses and the emergence of resistant strains.
Patients with an underlying focus in the bone or other organs, or infected with HIV, need to be treated for longer periods.6
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