A clinicoepidemiological study of cutaneous tuberculosis in a tertiary care teaching hospital in Andhra Pradesh, India

INTRODUCTION

Tuberculosis is as old as mankind, with evidence of the disease being found in a Peruvian mummy and in a skeleton from 300 BC. Globally 9.6 million new tuberculosis cases were detected in 2014 and 1.3 million deaths were attributable to the disease.¹ Tuberculosis is usually considered as disease of poverty as 94% of cases occur in countries with lower socioeconomic status. Though its incidence has fallen to 0.1% even in developing countries, the disease continues to be a formidable one because of human immunodeficiency virus (HIV) co-infection, drug resistance and atypical presentations.^2,3 The Present study was done to document the most common type of cutaneous tuberculosis, atypical presentations if any and response to directly observed short course (DOTS) therapy.

METHODS

All patients with clinically suspected cutaneous tuberculosis attending outpatient department of dermatology in our hospital from October 2012 to April 2016 were included in the study. A detailed history of presenting illness and thorough general, systemic and cutaneous examination was carried out along with documentation of demographic details. Routine blood investigations, enzyme linked immunosorbent assay (ELISA) for HIV, X-ray chest, mantoux test and biopsy were done in all cases. Sputum examination for acid fast bacilli (AFB), fine needle aspiration cytology of lymph nodes and other radiological tests were done in relevant cases. Diagnosed cases were given DOTS for a period of 6 months and response was assessed at 6 weeks and at the end of the therapy, side effects if any were also noted during the treatment period.

RESULTS

A total of 25 cases of cutaneous tuberculosis were included in the study. Male to female ratio in our study was 1.5:1. Age group of the study population ranged from 5-40 years with the mean age being 25 years 6 months. Most commonly involved site was the lower limb which was seen in 13 cases [52%]. The most common clinical type of cutaneous tuberculosis was lupus vulgaris seen in 11 cases (44%) and the least common was erythema induratum of bazin seen in 2 cases(8%), details are given in the Table 1.

HIV association was found in 3 cases (12%). Atypical presentations noted during the study were multifocal lupus vulgaris (LV), co-existence of tuberculosis verrucosa cutis (TVC) and LV, TVC of lower lip, erythema induratum of bazin (EIB) presenting as annular plaque in one case and as erythema nodosum in another case as shown from Figure 1-5. Mantoux was positive in 84.2% of the cases and typical histopathology was seen in 90% of the cases. Table 2 shows details of laboratory investigations of the study population. DOTS was effective in all cases except in 2 (8%) patients and truncal acne was observed in 2 (8%) patient as shown in Figures 6 and 7.

DISCUSSION

Cutaneous tuberculosis showed a higher incidence in men in our study similar to majority of the Indian studies.^4-6 This may be attributed to higher risk of sustaining injury in men, as many of our patients were involved in heavy manual work. Most of the patients were in their second decade, similar to that observed in other Indian studies.^6,7 The most common clinical type of cutaneous tuberculosis in our study was lupus vulgaris [44%], this was similar to few studies.^5,6,8 However few other Indian studies found scrofuloderma as the most common type and Table 3 shows the details.^7,9,10

We found lower limb as the most common involved site, it was also noticed by few authors.^6,8 High incidence of cutaneous tuberculosis on the legs in Indians can be explained by the re-inoculation of tuberculosis bacilli through minor trauma, especially during squatting.

Cutaneous tuberculosis was earlier quoted by Pillsbury, Shelly and Kligman as “in the skin tuberculosis presents itself in an astonishing variety of forms”.¹¹ correspondingly we observed various atypical presentations during our study. Multifocal lupus vulgaris was seen in a 40 year old male, there are very few reports of multifocal disease in the literature.^12,13 Multifocal involvement is mostly seen in unvaccinated and malnourished patients and usually have negative mantoux test. There are few reports of co-existence of different tuberculosis in the same person with combination of TVC and scrofuloderma [SFD] being most commonly reported including ours.^14,15 Immunohistological study of granuloma in cutaneous tuberculosis have shown a spectrum of changes as evidenced by CD4±CD8 ratio, i.e LV with strong immunity, TVC with intermediate immunity and SFD with low-level immunity.¹⁶ Depending up on the level of immunity in a person over a period of time, may be different types of cutaneous tuberculosis are expressed. Another probable reason is, TVC may develop from auto-innoculation of bacilli from adjacent cutaneous tuberculosis that is SFD. We found TVC of lower lip in a 40 year old female which is an uncommon site, few uncommon sites already reported in the literature are finger, over a keloid etc.^17,18 EIB clinically resembled erythema nodosum in one case. A similar observation was made by Maharaja et al in his study of the clinicohistopathological features of erythematous tender nodules predominantly involving the extremities, in which histological disacordance of erythema nodosum was seen in 8 cases [total 30 cases] and among them 3 cases were suggestive of EIB.¹⁹ Another atypical presentation of EIB noted in our study was a large annular plaque over thigh in a 25 year old male. So, EIB may not always present as classically described (ulcerating nodules on calves), it is the histopathology that helps in definitive diagnosis and differentiation.

Positive mantoux was seen in 84.2% of the cases, this was comparable to Binod kumar et al study, different results were seen in other studies, details given in Table 4.^7,8,20

Typical histopathological changes were seen in 90% of cases similar to other Indian studies.²⁰ Duration of antitubercular therapy [ATT] for cutaneous tuberculosis ranged from 6-12 months in different studies.^20-22 We employed DOTS therapy which was given for 6 months.

In Raghu Rama Rao et al study on DOTS therapy in cutaneous tuberculosis, efficacy was comparable with the standard daily short course chemotherapy with added advantage of exposure to less number of drugs, standard drugs being given under supervision and less travel expenses.²¹ He made the observation of no treatment failure or significant side effects with DOTS therapy in his study.²¹ In contrast we observed treatment failure in 8% of cases and minor side effects like truncal acne in 8%, details given in Table 5.

The duration of therapeutic trial in case of suspected cutaneous tuberculosis is 5-6 weeks, with the exception of tuberculids and patients showing minimal clinical activity before treatment. The diagnosis used to be reviewed in patients who didn't respond by this time. But with the advent of multi drug resistant (MDT) tuberculosis, this approach is not justified. MDR cutaneous tuberculosis should always be kept in mind in the management of patients with lack of clinical response to the first line ATT drugs or in those patients showing clinical deterioration even while on ATT. The definitive diagnosis of MDR tuberculosis is difficult owing to poor isolation rates and low sensitivity of molecular diagnostic tests. So it is always justified to give a trial of second line ATT for atleast two months before labelling a patient non responsive to therapy.²³ We had one wellbuilt (height 6 feet, weight 120 kg) 40 year old male patient with biopsy confirmed scrofuloderma who had not responded to routine dosages of ATT [AKT-4 kit] even after 5 weeks of therapy, thinking in terms of drug resistance before starting 2^nd line agents we gave him the first line agents adjusting to his per kg body weight. Within 2 weeks of hiking the dose the patient responded promptly, as presented in Figure 8. Hence, adequate drug dosing especially adjusted to the per kg body weight of a person is also most important before considering either alternative diagnosis or drug resistance.

To conclude, cutaneous tuberculosis is multifaceted. High clinical suspicion is necessary in rare presentations. Coexistence of two or more morphological patterns can occur. In doubtful cases, 5-6 weeks of therapeutic trail helps. Adequate dose is essential for good response. Second line drugs are to be considered in case of failure /clinical resistance.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. World health organisation, global tuberculosis report 2015. Available from http:// http://www.who.int/tb/publications/global_report/en/.
2. 2. Kumar B, Rai R, Kaur I, Sahoo B, Muralidhar S, Radotra BD. Childhood cutaneous tuberculosis: a study over 25 years from northern India. Int J Dermatol. 2001;40:26-32.
3. 3. Kumar B, Muralidhar S. Cutaneous tuberculosis: A-Twenty-year prospective study. Int J Tuberc Lung Dis. 1999;3:494-500.
4. 4. Kumar B, Kaur S. Pattern of cutaneous tuberculosis in North India. Indian J Dermatol Venereol Leprol. 1986;52:203-7.
5. 5. Acharya KM, Ranpara H, Dutta R, Mehta B. A clinicopathological study of 50 cases of cutaneous tuberculosis in Jamnagar district. Indian J Dermatol Venereol Leprol. 1997;63:301-3.
6. 6. Patra AC, Gharami RC, Banerjee PK. A profile of cutaneous tuberculosis. Indian J Dermatol. 2006;51:105-7.
7. 7. Thakur BK, Verma S, Hazarika D. A clinicopathological study of cutaneous tuberculosis at Dibrugarh district Assam. Indian J Dermatol. 2012;57:63-5.
8. 8. Puri N. A clinical and histopathological profile of patients with cutaneous tuberculosis. Indian J Dermatol. 2011;56:550-2.
9. 9. Sehgal VN, Srivastava G, Khurana VK, Sharma VK, Bhalla P, Beohar PC. An appraisal of epidemiologic, clinical, bacteriologic, histopathologic and immunologic parameters in cutaneous tuberculosis. Int J Dermatol. 1987;26:521-6.
10. 10. Gopinathan R, Pandit D, Joshi J, Jerajani H, Mathur M. Clinical and morphological variants of cutaneous tuberculosis and its relation to mycobacterium species. Indian J Med Microbiol. 2001;19:193-6.
11. 11. Pillsbury DM, Shelley WB, Kligman AM. Systemic bacterial infection. In: Dermatology. Philadelphia: WB Saunders; 1956: 499-540.
12. 12. Murugan S, Vetrichevvel TP, Subramanyam S, Subramanian A. childhood multicentric lupus vulgaris. Indian J Dermatol. 2011;56:343-4.
13. 13. Vora RV, Diwan NG, Rathod KJ. Tuberculosis verrucosa cutis with multifocal involvement. Indian Dermatol Online J. 2016;7:60-2.
14. 14. Rao AG. Scrofuloderma associated with tuberculosis verrucosa cutis. Indian J Dermatol Venereol Leprol. 2014;80:76-8.
15. 15. Sethuraman G, Kaur J, Nag HL, Khaitan BK, Sharma VK, Singh MK. Symmetrical scrofuloderma with tuberculosis verrucosa cutis. Clin Exp Dermatol. 2006;31:452-82.
16. 16. Sehgal VN, Gupta R, Bose M, Saha K. Immuno histopathological spectrum in cutaneous tuberculosis. Clin Exp Dermatol. 1993;18:309-13.
17. 17. Narayana GP, Sandhya I. Verrucous carcinoma of the finger: A rare site of occurrence. Indian Dermatol Online J. 2014;5:218-9.
18. 18. Kala S, Pantola C, Agarwal A. Tuberculosis verrucosa cutis developing over a keloid: A rare presentation. J Surg Tech Case Rep. 2010;2:75–6.
19. 19. Maharaja K, Khandpur S, Ramam M, Singh MK, Kumar U, Sharma VK. A study of the clinico-histopathological features of erythematous tender nodules predominantly involving the extremities. Indian J Dermatol Venereol Leprol. 2014;80:235-42.
20. 20. Dwari BC, Ghosh A, Paudel R, Kishore P. A clinicoepidemiological study of 50 cases of cutaneous tuberculosis in a teritiary care teaching hospital in Pokhara, Nepal. Indian J Dermatol. 2010:55:233-7.
21. 21. Raghu Rama Rao G, Sridevi, Lakshmy Narayan B, Amareswar A, Sandhya S. Directly observed treatment short course and cutaneous tuberculosis: Our experience. Indian J Dermatol Venereol Leprol. 2011;77:330-2.
22. 22. Ramesh V, Sen MK, Sethuraman G, D'Souza P. Cutaneous tuberculosis due to multidrug-resistant tubercle bacilli and difficulties in clinical diagnosis. Indian J Dermatol Venereol Leprol. 2015;81:380-4.
23. 23. Ramam M, Tejasvi T, Manchanda Y, Sharma S, Mittal R. What is the appropriate duration of a therapeutic trial in cutaneous tuberculosis? Further observations. Indian J Dermatol Venereol Leprol. 2007;73:243-6.