|Year : 2013 | Volume
| Issue : 2 | Page : 71-74
Multidrug resistant Mycobacterium tuberculosis in cutaneous tuberculosis in China
Xiaohua Tao1, Yanshi Mo2, Yang Guan2
1 Dermatology Hospital of Jiangxi Province, The Affiliated Dermatology Hospital of Nanchang University, Yingbin Road, Nanchang, Jiangxi Province, China
2 Shenzhen Chronic Disease Hospital, Buxin Road, Shenzhen, Guangdong Province, China
|Date of Web Publication||23-May-2014|
Dermatology Hospital of Jiangxi Province, The Affiliated Hospital of Nanchang University, Nanchang - 330 000, Jiangxi Province
Source of Support: None, Conflict of Interest: None
| Abstract|| |
We describe a male patient who presented with a 2 years history of recurrent ulcers and erythematous plaques on the buttocks. Skin biopsy and tissue culture on Lowenstein Jensen media resulted in the isolation of Mycobacteria, which was further identified as Mycobacterium tuberculosis (MTB) by polymerase chain reaction. The results of drug susceptibility tests showed that the MTB isolated was resistant to isoniazid (INH), rifampicin (RIF), ethambutol (ETH) and rifapentine (RFT). During 7 years of follow-up after discharge from hospital admission, the erythematous plaques and atrophic scars remained confined to the patient's buttocks. This is the first reported case of cutaneous multidrug-resistant tuberculosis (MDR-TB) in China. Given the increasing incidence of MDR-TB in china, our case report calls for heightened clinical awareness and improved facilities to confirm the diagnosis of MDR-TB.
Keywords: China, cutaneous, multidrug-resistant tuberculosis
|How to cite this article:|
Tao X, Mo Y, Guan Y. Multidrug resistant Mycobacterium tuberculosis in cutaneous tuberculosis in China. Ann Nigerian Med 2013;7:71-4
| Introduction|| |
The prevalence of tuberculosis (TB) in China has declined in recent years, however, the number of new cases of TB and the prevalence of multidrug-resistant TB (MDR-TB) have increased. , Emergence and spread of MDR-TB pose serious threats to TB control, and failure to effectively deal with MDR-TB could result in a rapid increase in the number of new cases.  This will have very serious negative consequences. Several cases of cutaneous MDR-TB have been documented in many countries in recent years. ,,,, We document the first reported case of cutaneous MDR-TB diagnosed in China, with a 7 years period of follow-up.
| Case Report|| |
The present case report is about a 41-year-old male non-resident worker who was presented to our clinic in 2005 with a 2 years history of recurrent ulcers and erythematous plaques on the buttocks. Five years prior to presentation, the patient had been diagnosed with pulmonary TB of the upper zone of the left lung and was treated with a daily regimen of 400 mg INH, 450 mg RIF and 750 mg ETH for 6 months. The patient was compliant with his treatment. About 2½ years after termination of anti-TB treatment, the patient had a reoccurrence of generalized malaise, dry cough and weight loss; and also reported the first incidence of ulcers on the buttocks. Within days, these lesions merged into large ulcers measuring about 1-5 cm in diameter. Chest X-ray (CXR) showed patchy infiltrates affecting the upper zone of the left lung. He was retreated with the same 6 months daily tri-drug regimen. During therapy, most of the damage to the affected lung tissue healed and the lesions on buttocks started to heal. There was no history suggestive of intestinal TB or a underlying cause of immunosuppression.
Dermatological examination revealed two erythematous plaques on the buttocks [Figure 1]. No lymphadenopathy was found on general examination and respiratory system examination detected no abnormality. CXR showed mild fibrotic lesions affecting the upper zone of the left lung. Result of the tuberculin skin test was positive (20 mm). Microscopic examination of scales from the lesion was negative for fungi. Decreased blood CD4 T-cell content of 25% (normal range 27-51%) and a decreased CD4/CD8 T-cell ratio of 0.68 (normal range 0.9-2) were reported. A skin biopsy was taken from the lesion on the left buttocks. On histopathological examination, the biopsied tissue demonstrated epidermal hyperkeratosis, parakeratosis and irregular epidermal hyperplasia in the epidermis; and profound leucocyte and monocyte infiltration with several peripheral multinuclear giant cells in the dermis [Figure 2]. Ziehl-Neelsen staining for detection of acid-fast bacilli (AFB) was negative. Tissue culture on Lowenstein Jensen media resulted in the isolation of mycobacteria. The mycobacterial deoxyribonucleic acid (DNA) was extracted and purified from the culture. Polymerase chain reaction (PCR) and sequencing of the 16S-23S ribosomal ribonucleic acid (rRNA) internally transcribed spacer region was performed using primers Sp1 (5'-ACC TCC TTT CTA AGG AGC ACC-3') and Sp2 (5'-GAT GCT CGC AAC CAC TAT-3').  The 16S-rRNA sequence identified the mycobacteria as Mycobacterium tuberculosis (MTB). Drug susceptibility tests (DSTs) showed resistance to INH, RIF, ETH and rifapentine, indicating MDR-TB. Screening for hepatitis viruses A-E, syphilis and human immunodeficiency virus (HIV) were negative.
|Figure 2: Profound leucocyte and monocyte infiltration and some peripheral multinuclear giant cells in the dermis of the patient (H and E, ×100)|
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Based on the clinical and laboratory findings, a diagnosis of lupus vulgaris caused by MDR-TB was made. A thorough discussion with the patient about his diagnosis, prognosis and toxicity associated with the use of anti-TB agents led to him making an informed decision to defer treatment. During the 7 years of follow-up (inspection of the lesion and X-ray every 3 months), the patient has remained healthy, except for the residual erythematous plaques and atrophic scars on the buttocks.
| Discussion|| |
Cutaneous TB is a rare form of TB comprising about 2.4% of all types of TB.  We performed a computer-assisted search of the literature (through the PubMed database and China National Knowledge Infrastructure) and identified 5 reports of cutaneous MDR-TB. The first report of cutaneous MDR-TB was described in 1995.  Since then, 4 other reports have been published. The 5 reports consisted of 10 patients of whom 8 had MDR-TB culture results. All the 8 patients were male and 4 (50%) were HIV positive [Table 1]. In China, only an estimated 20% of TB patients take their anti-TB medications regularly.  Our patient had a history of pulmonary TB and no history local trauma. His DSTs indicated drug resistance that was in accordance with initial use of those drugs. Thus, we conclude that the emergence of MDR-TB in our patient was likely induced by his treatment regimens.
|Table 1: Cases of cutaneous tuberculosis caused by multidrug-resistant mycobacteria reported from across the globe|
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The bacillary load in cutaneous TB is usually less than that in pulmonary TB, which makes diagnosis of cutaneous TB challenging. AFB microscopy is the most commonly used rapid and inexpensive screening test; however, it has a sensitivity of only 53% in diagnosis of active disease.  Histopathological diagnosis of cutaneous TB usually depends on the presence of granulomatous inflammation and caseous necrosis. Histology, however, cannot distinguish cutaneous TB from infections caused by non-TB mycobacteria and mycobacteria leprae. Histology can also not distinguish cutaneous TB from some granulomatous diseases such as sarcoidosis and systemic lupus erythematosus, except for when AFB is detected in the specimen. Culture is, therefore, essential for a definitive diagnosis. However, the organism takes weeks to grow before for identification; and its sensitivity is relatively low in cutaneous TB, because of its paucibacillary nature. Recently, response to anti-TB therapy has been recommended as an alternative standard in diagnosing cutaneous TB; especially when a patient is suspected of having the disease, but a definitive diagnosis cannot be made by the present diagnostic methods.  The patient can undergo a 5 weeks therapeutic trial. Patients who have not responded by this time are unlikely to do so with further treatment and should have their diagnosis reviewed. However, therapeutic trial can lose its value if there is a high likelihood of MDR-TB.
Nucleic acid amplification tests can detect nucleotide sequences unique to MTB directly in specimens and give results within few hours, thus offering better accuracy than AFB smear microscopy and greater speed than culture.  Moreover, Xpert MTB/RIF uses PCR assay to amplify the rpoB gene, which is probed with molecular beacons for mutations within the RIF-resistance determining region.  This test can provide sensitive detection of TB and RIF resistance directly from untreated sputum in less than 2 h, with minimal hands-on time.  Since bacterial messenger RNA (mRNA) has a mean half-life of 3-5 min and is more prone to destruction than genomic DNA, a positive mRNA signal indicates the presence of viable organisms. 
Most cases of TB of the skin are related to TB of other organs. The bacillary load in the skin is usually less than that in other areas, so treatment regimens, such as those used to treat pulmonary TB, should be sufficient for treating cutaneous TB.  In our report, however, it seems that the therapy mentioned above was sufficient for treating pulmonary TB, but insufficient for cutaneous TB treatment. The underlying mechanism for this phenomenon should be further studied.
| Conclusion|| |
As the spread of MDR-TB continues, more cases of cutaneous MDR-TB are likely to be encountered by physicians. This case report underscores the need to be aware of this entity, so that early diagnosis and specific therapy can be instituted promptly.
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[Figure 1], [Figure 2]