On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.5 Rio de Janeiro Sept./Oct. 2004
CLINICAL, EPIDEMIOLOGICAL, LABORATORY AND THERAPEUTIC INVESTIGATION
Correlation between clinical and laboratorial findings of the leprosy cases followed at the "Alfredo da Matta" Dermatology Center, Manaus-AM, Brazil, from January 2000 to March 2001, based on secondary data*
Iara L. F. CrippaI; Maria Conceição SchettiniI; Antonio P. SchettiniII; Silmara N. PenniniIII; Paula F. Bessa RebelloIV
IMD, dermatologist at Fundação
Alfredo da Matta
IIMD, dermatologist at Fundação Alfredo da Matta/MSc in tropical pathology
IIIMD, dermatologist at Fundação Alfredo da Matta/ MSc in Public health/epidemiology
IVMD, dermatologist at Fundação Alfredo da Matta/ MSc in Public health/epidemiology
BACKGROUND: the World Health Organization
(WHO) and the Brazilian Health Ministry recommend the adoption of the operational
classification for therapeutic purposes (multi- or paucibacillary). The validity
of that classification is discussed taking as a reference the results of bacilloscopic
OBJECTIVE: To verify the sensitivity and specificity of the operational clinical classification that takes into account exclusively the number of cutaneous lesions and that which considers the thickening of neural trunks as well as the number of cutaneous lesions, and relating these with the results from the bacilloscopic exam.
METHODS: The information source was consultation of the records referring to patients with a diagnosis of leprosy, from January 2000 to March 2001, at the Fundação Alfredo de Matta, in Manaus, AM. The demographic, clinical and laboratorial data were compiled.
RESULTS: The clinical classification based exclusively on the number of cutaneous lesions showed a sensitivity of 73.6% and specificity of 85.6% regarding the bacilloscopy. The classification that combines the number of cutaneous lesions and neural thickening demonstrated 75.8% sensitivity and 71.8% specificity.
CONCLUSION: The clinical classification of leprosy based on the number of cutaneous lesions showed, in this work, sensitivity and specificity values similar to those described in studies done in other countries. When the classification was broadened to include the other clinical parameter (the presence of thickened peripheral nerves) there was a significant decrease in the specificity, without a statistically significant increase in sensitivity.
Key words: leprosy; leprosy/classification; sensitivity; specificity
The World Health Organization (WHO) recommends that in regions where good quality bacilloscopy is not available, the leprosy patients should be classified, for treatment purposes, according to the number of cutaneous lesions, considering paucibacillary to be those with up to five lesions and multibacillary to be those with more than five lesions.1 Although cutaneous bacilloscopy is still the gold standard for this purpose, with the decentralization of the control program, a large part of the patients are seen at peripheral health care centers, which, in general, do not have the physical structure, equipment, materials and technical personnel qualified to perform good quality bacilloscopic exams2
Other systems for clinical classification have been proposed, such as that initially recommended by the Brazilian Health Ministry (HM), that took into account the number of cutaneous lesions and/or nerve trunks involved3,4,5 (Chart 1).
The different systems of clinical classification present disparities in their capacity to detect multibacillary forms (sensitivity) and to correctly identify paucibacillary forms (specificity). Classifications that demonstrate little specificity cause a great number of paucibacillary patients to be included in multibacillary treatment regimens, with serious consequences from the perspective of the individual and public health services: there will be unnecessary exposure of patients to potentially toxic drugs; the diagnosis will lead to psychosocial problems due to the stigma; and the control program will suffer increased costs through the waste of erroneously prescribed drugs. While those that demonstrate little sensitivity cause a significant number of multibacillary patients to be treated in an inadequate manner, which is more serious, since it allows the progression of the disease in the individual and exposes the community to a potential transmission source (Chart 2).
Attempts at a concomitant improvement in sensitivity and specificity of the classification, by introduction of more clinical parameters and addition of complementary exams, have not demonstrated satisfactory results. The increase in sensitivity promotes a decrease in specificity, and vice-versa, while the addition of new technology cannot be absorbed at the most elementary levels of the health care structure.
The present study intends to evaluate, in a sample of leprosy patients resident in an endemic area, the sensitivity and specificity of the clinical classification recommended by WHO, taking the result of the bacilloscopy to be the gold standard, as well as to verify whether the increment of another variable, namely the number of thickened nerves, contributes to improved accuracy of the classification.
MATERIAL AND METHODS
The study was developed in a reference center for leprosy, located in the city of Manaus, AM, Fundação Alfredo de Matta - Fuam, historically responsible for the diagnosis of approximately 50% of the new cases of leprosy in the Amazon State. The source of information was the records of patients with a diagnosis of leprosy from January 2000 to March 2001, from which the demographic, clinical and laboratorial data were registered, according to the routine of the Center, that counts on a team of specialized professionals with experience in the diagnosis and treatment of the disease. In this period, 634 new cases of leprosy were diagnosed, of which only six were not included in the study because the records did not include the results from bacilloscopy.
The bacilloscopic exam was performed with smears of lymph from skin of five locations in each patient: ear lobes, elbow folds and cutaneous lesions. The staining technique and reading followed recommendations by the Brazilian Health Ministry.4
The evaluation of sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) of the clinical classifications, with the respective 95% confidence intervals (95% CI), were performed taking the reference pattern to be the result of the skin bacilloscopy and using Epi Info 6 software.
A total of 628 patients were included with age from three to 82 years, 69 (11%) less than 15 years, and 559 (89%) 15 years or over. The mean age was 33.7 years (SD 18.2 years), and 64% of the patients were male.
Regarding the skin bacilloscopy, 178 (28.34%) presented a positive result, and 450 (71.66%) were negative.
According to the clinical classification recommended by WHO, 196 (31.21%) patients were multibacillary, considering that they presented more than five skin lesions, and 432 (68.79%) with up to five lesions were classified as paucibacillary. The sensitivity, in relation to the result of the bacilloscopy, was 73.6% (95% CI 66.4-79.8), and the specificity was 85.6% (95% CI 81.9-88.6). The positive predictive value was 66.8% (95% CI 59.7-73.3), and the negative predictive value was 89.1% (95% CI 85.7-91.8) (Table 1).
When the classification was broadened to include the criterion of presence of thickened peripheral nervous trunks, the sensitivity was 75.8% (95% CI 68.8-81.8), and specificity was 71.8% (95% CI 67.3-75.8), with PPV 51.5% (95% CI 45.3-57.7) and NPV 88.3% (95% CI 84.4-91.3) (Table 2).
Table 3 shows the comparison between the values obtained for sensitivity, specificity, PPV and NPV, when used together, for the clinical classification, the number of cutaneous lesions and the presence of nerve trunk involvement, in relation to the result from the cutaneous bacilloscopy. It was verified that there is an increase in sensitivity, although without statistical significance at the 5% level. In relation to specificity, a statistically significant decrease was observed.
The clinical classification of leprosy recommended by WHO offers easy applicability and low cost so won rapid acceptance among the various control programs for the disease, and is even used in reference centers that have good quality bacilloscopic exam available.6 The evaluation of the sensitivity and specificity of the different classifications, using a standard test such as bacilloscopy as a reference, is fundamental to validate its use and is of great importance, because even if a single treatment scheme is adopted, it is nevertheless of great value to determine which are pauci- or multibacillary, since the prognostic and clinical management can be different. Various studies have been carried out with this aim, however a comparative analysis between them is rendered difficult due to the different criteria used for the clinical classification and to the use, at times of bacilloscopy and at other times of histopathology, as the reference standard.
Becx-Bleumink7 evaluated a classification that considered multibacillary patients to be those that present more than five cutaneous lesions and compared the results with the bacilloscopy exam, considering multibacillary to be those that presented a bacilloscopic index (BI) greater than one. The data analysis showed 92% sensitivity and 42% specificity.
Groenen et al .9 and van Brakel et al .8,9 obtained similar results (92% sensitivity and 41% specificity in the former, and 93% sensitivity and 39% specificity in the latter study), using different clinical criteria and comparing the clinical classification with the result of the bacilli tests in the histopathological exam of skin biopsies.
These studies demonstrated in common a good sensitivity to detect multibacillary cases, but low specificity, such that a large number of paucibacillary patients would be treated with the multibacillary regimen. Groenen et al.9 attempted to improve the specificity by trying combinations of different clinical criteria, but they were not successful, because the increase in specificity always occurred in detriment to the sensitivity.
Croft et al .,10 Dasananjali et al .11 eand Buhrer-Sekula et al .,12 using the classification proposed by WHO, obtained similar values, differing from the first studies by demonstrating an increase in the specificity, but lower sensitivity. Despite the improvement in the specificity values, the fall in sensitivity meant that a considerable number of patients with positive bacilloscopy were classified as paucibacillary and thus were treated inadequately. Dasananjali et al .11 have suggested that the group of patients inadequately classified as paucibacillary would be at greater risk of recurrence, due to insufficient treatment.
In the present study, when using the classification criterion based solely on the number of cutaneous lesions, it was verified that the values for sensitivity and specificity were close to those found by the last three authors. It was found that 47/178 (26.4%) patients with positive bacilloscopy would be erroneously classified as paucibacillary, with harmful consequences for the patients and for the control program of the disease.
Buhrer-Sekula et al .,12 in a study also carried out in Brazil, tried to improve the sensitivity, by increasing the clinical criterion to include testing for anti-PGL-i antibodies and obtained good results; however a small number of multibacillary patients would receive incorrect treatment, besides which, additional material and training resources would be necessary to perform the antibody tests.
In the present study, we aimed at verifying the possibility of improving sensitivity to detect the multibacillary forms, using the criterion of number of cutaneous lesions together with the presence of thickened nerve trunks, since neural thickening is more common in the multibacillary forms.13 The data showed that this strategy enabled an increased sensitivity, but without statistical significance at the 5% level. There was a statistically significant decrease in specificity, and in this manner the situation of improving one parameter (sensitivity) to the detriment of the other (specificity) was repeated. Besides which, by adding a new criterion (presence of thickened nerve trunks), it was necessary to train the health teams for this evaluation. Nowadays, neither the classification proposed by WHO nor that recommended by the Brazilian Ministry of Health consider the number of thickened nerve trunks in the classification.
Thus the results of the present study are in agreement with previous studies published and also demonstrate the necessity to look for new parameters, with simple implementation, that would allow improved sensitivity in the detection of multibacillary cases, without significant detriment to specificity.13,14 Good quality bacilloscopic exam, that potentially reaches 100% sensitivity and specificity13 still seems irreplaceable for the correct allocation of the various treatment regimes, while the classification based only on clinical criteria should be restricted to places where this exam is not available.
The clinical classification of leprosy recommended by WHO, when compared to the results of the bacilloscopic exam, presented sensitivity and specificity of 73.6% (95% CI 66.4-79.8) and 85.6% (95% CI 81.9 88.6), respectively. The concomitant use of another clinical parameter, the presence of peripheral nerve involvement, lead to a significant decrease in the specificity, at the 5% level, without a significant increase in sensitivity. Therefore, it is only justifiable to use this clinical classification in regions where bacilloscopy is not available.
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Received on May 28, 2004.
Approved by the Consultive Council and accepted for publication on August 31, 2004.
* Work done at Fundação Alfredo da Matta, leprosy and sexually transmitted disease reference center, in Manaus, AM.