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- Patients and methods
- Patients’ characteristics
Objective To define the bacteriological and histological correlates of the three predominant clinical forms of cutaneous tuberculosis and to evaluate the efficacy of a 9-month daily regimen containing rifampicin and isoniazid.
Methods In the dermatological clinics of two major teaching hospitals in Chennai, 213 patients with suspected clinical manifestations of cutaneous tuberculosis underwent examination and a skin biopsy for bacteriological and histological tests. They were treated with a daily regimen of rifampicin and isoniazid for 9 months and follow-up for 3 years.
Results Bacteriological and/or histological confirmation of tuberculosis was obtained in 88% of the cases. Lupus vulgaris lesions were seen mainly in the extremities and verrucosa cutis occurred predominantly on the sole and foot, while the cervical and axillary regions were the commonest sites for scrofuloderma. Ninety-two per cent of the patients showed resolution of the lesions within the first 6 months of chemotherapy; 1% failed to respond to this regimen. There was no relapse in any of the cases during the follow-up period of 3 years.
Conclusions Clinical findings were adequate to identify major forms of cutaneous tuberculosis as evidenced by bacteriological and histopathological examination. A daily regimen of rifampicin and isoniazid for 9 months was effective in treating cutaneous tuberculosis.
Objectifs Définir les corrélations bactériologiques et anatomopathologiques des trois formes cliniques prédominantes de la tuberculoses cutanée et évaluer l'efficacité d'un traitement journalier de 9 mois contenant de la rifampicine et de l'isoniazide.
Méthodes A partir des consultations de dermatologies de deux grands hôpitaux universitaires à Chennai, 213 patients avec une suspicion clinique de tuberculose cutanée ont bénéficié d'un examen clinique et d'une biopsie cutanée pour des examens bactériologiques et anatomopathologiques. Ils ont été traités par un traitement journalier de rifampicine et d'isoniazide durant 9 mois et suivis pendant 3 ans.
Résultats la confirmation bactériologique et/ou anatomopathologique de tuberculose était obtenue dans 88% des cas. Des lésions de lupus vulgarisétaient présentes le plus souvent aux extrémités et de verrucosa cutis de façon prédominante sur la plante et sur le pied, alors que les régions cervicales et axillaires étaient les sites habituels pour les gommes tuberculeuses. 92% des patients ont vu leur lésion disparaître dans les 6 premiers mois du traitement ; 1% n'ont pas répondu à ce traitement. Il n'y a eu aucune rechute dans les 3 années de suivi.
Conclusions Les éléments cliniques sont adéquats pour identifier les formes majeures de tuberculose cutanée comme en témoigne l'examen bactériologique et anatomopathologique. Un traitement journalier de rifampicine et d'isoniazide de neuf mois est efficace dans le traitement de la tuberculose cutanée.
Mots clefs tuberculose cutanée , rifampicine , isoniazide , diagnostic bactériologique/anatomopathologique , diagnostic clinique , Inde
Objetivo Definir la correlación bacteriológica e histológica de las tres formas clínicas predominantes de la tuberculosis cutánea, y evaluar la eficacia de un régimen diario de 9 meses de duración de rifampicina e isoniazida.
Métodos En las clínicas dermatológicas de dos importantes hospitales universitarios en Madrás (Chennai), 213 pacientes con sospechadas manifestaciones clínicas de tuberculosis cutánea fueron examinados, y se les realizaron biopsias de piel para análisis bacteriológicos e histológicos. Fueron tratados con un régimen diario de rifampicina e isoniazida durante 9 meses, y controlados durante 3 años.
Resultados Se obtuvo una confirmación bacteriológica y/o histológica de tuberculosis en 88% de los casos. Lesiones de Lupus vulgar fueron observadas principalmente en las extremidades, y cutánea verrucosa predominantemente en la planta y pie, mientras que las regiones cervicales y axilares fueron los lugares más comunes de escrofuloderma. 92% de los pacientes mostró una resolución de sus lesiones dentro de los primeros 6 meses de quimioterapia; un 1% no respondió a este tratamiento. No hubo recaída en ninguno de los casos durante el siguiente período de control de 3 años.
Conclusiones Los hallazgos clínicos fueron adecuados para identificar las formas más importantes de tuberculosis cutánea, como quedó evidenciado por los exámenes bacteriológicos e histológicos. Un régimen diario de rifampicina e isoniazida durante nueve meses fue efectivo en el tratamiento de la tuberculosis cutánea.
Palabras clave tuberculosis cutánea , rifampicina , isoniazida , diagnóstico bacteriológico/histológico , diagnóstico clínico , India
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- Patients and methods
- Patients’ characteristics
During the period of intake (from 27 December 1993 to 17 November 1998), 330 patients presented with clinical features consistent with a diagnosis of cutaneous tuberculosis. This constituted 0.125% of the total out patient attendance in the Dermatology Departments of the two hospitals during this period. Of these, 99 patients were unwilling to participate in the study. Of the 231 patients registered, four had carcinoma, two had sputum smear positive pulmonary tuberculosis, two were HIV positive, two died because of non-tuberculous causes. Eight patients who presented with crops of hard, dusky, non-itchy symmetrical, multiple papules were diagnosed as having papulo necrotic tuberculid. These patients were excluded as histopathology and culture for M. tuberculosis were negative and molecular biological and/or immunological tests were not performed. Thus, a total of 213 patients remained in the study.
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- Patients and methods
- Patients’ characteristics
The proportion of cutaneous tuberculosis amongst the outpatients attending the dermatology departments of the major teaching hospitals in Chennai appears to be extremely low – 0.125% in this study. This is similar to the figures reported by Mammen and Thumbiah (1974) in the same area approximately 30 years ago. This is also in agreement with that reported by others (Sehgal et al. 1987; Kumar & Muralidhar 1999).
It is generally believed that in extra pulmonary tuberculosis, there is a greater preponderance in adult females as observed in tuberculous lymphadenitis (Ramanathan et al. 1999). However, in cutaneous tuberculosis, there appears to be a greater prevalence in men (3:1) as seen in data from the study and also as reported by others (Sehgal et al. 1987; Kumar & Muralidhar 1999). This is similar to pulmonary tuberculosis (Khatri & Freiden 2000). However, this ratio varied from type to type. In patients with lupus vulgaris, the ratio was 2.3:1, in verrucosa cutis 6.8:1 and in scrofuloderma 1.5:1. The male preponderance in verrucosa cutis was significantly higher compared with scrofuloderma (χ2 = 7.285; P < 0.01) and lupus vulgaris (χ2 = 6.693; P < 0.01). However, the distribution of the sexes was comparable in lupus vulgaris and scrofuloderma (P > 0.05). It was found that the proportion of children (below12 years) was 24.4% (52 of 213) which is similar to that reported by Arora and Agarwal (2005). Further, in children below 12 years, scrofuloderma was significantly more than lupus vulgaris (P < 0.05) and verrucosa cutis (P < 0.01) irrespective of the sex.
We found larger proportions of individuals with verrucosa cutis compared with other Indian studies in both adults and children. This could be due to the fact that these lesions were seen mainly in the sole and foot and could be attributed to the practice of many individuals walking bare foot in this part of the world.
Patients with scrofuloderma presented earlier compared with lupus vulgaris and verrucosa cutis. This could be due to the fact that in cutaneous tuberculosis, none of the patients had any constitutional symptoms and locally in lupus vulgaris and verrucosa cutis, the lesions were non-itchy and painless. However, in scrofuloderma, the discharging sinus was physically uncomfortable and occasionally painful and hence these patients could have reported earlier.
Although the lesions in all the three types of cutaneous tuberculosis were seen over the entire body, there appeared to be some marked differences in their distribution. Lupus vulgaris was observed largely over the extremities (61 of 110) and verrucosa cutis was seen predominantly in the sole and foot (50 of 78), while in scrofuloderma, it occurred mainly over the lymph nodes (17 of 25). Further, lupus vulgaris and scrofuloderma, lesions did not occur on the sole of the foot while verrucous lesions were absent over the face. The pathogenic mechanisms responsible for this differential distribution need to be explored. One possible mechanism may be infection because of direct inoculation. For example, in the present study, there was history of injury over the lesion in 14 of 110 cases in lupus vulgaris, 9 of 77 in verrucosa cutis and 3 of 25 in scrofuloderma.
On the whole, scrofuloderma lesions were much smaller than lupus vulgaris or verrucosa cutis lesions. Again this could be due to the discharging sinus which prompts the patient to seek medical help earlier. A similar association between the duration of the disease and size of the lesion in lupus vulgaris has been reported by Horwitz and Christensen (1960).
X-ray lesions suggestive of pulmonary tuberculosis were seen in six cases (one scrofuloderma, two lupus vulgaris and three verrucosa cutis), although all of them were bacteriologically negative. Further, in none of the cases, there was clinical evidence of disseminated tuberculosis. This is unlike that reported by Kumar and Muralidhar (1999) who found that scrofuloderma represents a more disseminated form of the disease. Similarly, unlike skin tuberculosis, in other forms of extra pulmonary tuberculosis, there is evidence of disseminated disease (Balasubramaniam & Ramachandran 2000)
There was no difference in the yield of culture positivity in the three types of cutaneous tuberculosis. Although it is widely believed that it is difficult to demonstrate viable bacilli in a paucibacillary condition like cutaneous tuberculosis (Michelson 1948; Sehgal et al. 1987) culture positivity rate was 55% in the present study. This could be due to the use of multiple media for culture and the use of Kirchner's liquid medium for preserving the biopsy material till they were processed as has been performed in non-cutaneous tuberculosis (Mitchison et al. 1983; Vanajakumar et al. 1997). Thus, findings from this study, therefore, belie the popular impression that culturing of cutaneous lesions for M. tuberculosis could be tedious and unrewarding (Sehgal et al. 1987).
The drug resistance pattern including initial multi drug resistance (to isoniazid and rifampicin) of the isolated tubercle bacilli in this study is similar to the resistance pattern seen among new pulmonary tuberculosis patients admitted recently to various controlled clinical trials at this centre (Tuberculosis Research Centre 2002, 2004). Although multidrug resistant tuberculosis was not observed in our earlier studies conducted on extra pulmonary tuberculosis, our recent study in patients with tuberculous lymphadenitis (Jawahar et al. 2005) shows that multidrug resistant tuberculosis is similar to the present findings of 2%.
The histopathology of the lesions seen was typical of tuberculous granuloma although caseation necrosis was absent in all cases of verrucosa cutis and in an overwhelming majority of lupus vulgaris cases. This finding is in marked contrast to that reported by Sehgal et al. (1987). The presence of moderate numbers of plasma cells in lupus vulgaris and scrofuloderma indicates that these cells as well as humoral immune response probably play a role in the pathogenesis of these types of cutaneous tuberculosis. A similar association of plasma cells in some forms of tuberculous lymphadenitis has been reported earlier (Ramanathan et al. 1999).
Correlation of histopathology with bacteriology results indicates that these two indices are complementary to each other and performing these two diagnostic procedures increases the establishment of the diagnosis of cutaneous tuberculosis by 8%.
As cutaneous tuberculosis is a pauci bacillary condition, we initiated patients on a 9 months daily rifampicin and isoniazid regimen. It is noteworthy that in nearly half the patients the lesions resolved in 3 months and in 92% by the sixth month. Further, in this series, 12 of the 14 patients who had resistance to any of the drugs either alone or in combination, had no failure or relapse of the condition during the 3-year follow-up period. However, no definite conclusion could be drawn about the effectiveness of this regimen where resistance to rifampicin was seen. In one patient who had isolated rifampicin resistance, the lesion resolved. Of the two patients who had resistance to rifampicin and isoniazid, one died of non-tuberculous cause and the other patient defaulted after completion of treatment and was lost for further follow-up. Overall, in this series it was observed that though there was bacteriological resistance, clinical resolution could be achieved even with a two drug regimen. It was also noted that irrespective of the type, size or duration of the lesion, complete resolution occurred. These findings are in agreement with those made earlier in other forms of extra pulmonary tuberculosis (Balasubramaniam & Ramachandran 2000). In view of the success of this two-drug, 9-month regimen, a further shortening of the treatment duration can be achieved by the inclusion of an additional drug.