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Lupus vulgaris
Lupus vulgaris Clinical} histopathologic, and bacteriologic study of 10 cases Joaquim Marcoval, MD,a Octavia Servitje, MD,a Abelardo Moreno, MD,b Anna Jucgli, MD,a and Jordi Peyri, MDa Barcelona, Spain
Background: Lupus vulgaris (LV) represents the most common form of cutaneous tuberculosis in Europe. However, recent reports from European countries are few and usually limited to isolated cases. Objective: We report the clinical, histopathologic, and bacteriologic data in 10 patients with LV. Methods: The diagnosis of LV was made according to a combination of clinical, histologic, and bacteriologic criteria. In each case a biopsy specimen was obtained for histopathologic study and mycobacteriologic culture. All but one patient received a 9-month course of combined antituberculous therapy. Results: Five patients had evidence of either previous or simultaneous tuberculous foci other than LV. Mycobacterium tuberculosis was isolated from cutaneous lesions in five cases. The histologic study revealed a variable granulomatous reaction, including tuberculoid granulomas, sarcoidlike granulomas, and a "mixed" granulomatous reaction. Conclusion: Although different mechanisms could be implicated in the development of LV, an association with visceral tuberculosis is not infrequent. Combined antituberculous therapy should be the treatment of choice in these patients. (J AM ACAD DERMATOL 1992;26:404-7.) The incidence of cutaneous tuberculosis has been progressively decreasing in industrially developed countries during this century. 1,2 Improved hygiene and living standards as well as antituberculous therapy are responsible for this change. 3 However, infections caused by mycobacteria are still common in some areas. Large series have been reported from Asia3-6 while recent reports from developed countries are usually limited to isolated cases. We examined the records of lO patients with lupus vulgaris (LV), the most common form of cutaneous tuberculosis in Europe.5-10
PATIENTS AND METHODS Ten patients (four men, six women; age ranging from 24 to 77 years) with LVdiagnosed from 1985 to 1990 are included. The diagnosis of LV was made according to a combination of criteria including chronic cutaneous
From the Departments of Dermatology" and Pathology,b Hospital "Princeps D'Espanya." Accepted for publication Sept. 23, 1991. Reprint requests: Joaquim Marcoval, MD, PzTetuan 38-39 II 2,08010 Barcelona, Spain.
16/1/33976
404
plaques with "apple jelly" nodules, an inflammatory granulomatous reaction on histologic examination, microbiologic findings, presence of active tuberculosis elsewhere, the results of the Mantoux test, and response to antituberculous therapy. The Mantoux test was performed in all patients by injecting intradermally 5 TV of commercially available tuberculin. Other routine investigations included complete blood cell count, total and differential leukocyte count, erythrocyte sedimentation rate, and chest roentgenography. In each case a biopsy specimen oflesional skin was obtained. Half the specimen was cultured in LowensteinJensen medium. The other half was formalin-fixed and processed by routine methods. The histologic sections were stained with hematoxylin-eosin and special stains for acid-fast bacilli. All but one patient were treated with a 9-month course of isoniazid (5 to 10 mg/kg/day) and rifampicin (10 to 20 mg/kg/day) supplemented by a 3-month initial phase of ethambutol (15 to 25 mg/kg/day). Patient 5 was also treated by drainage of a supraclavicular adenitis. In patient 1 the lesion was surgically excised as the only form of therapy.
RESULTS
Clinical features The clinical and bacteriologic data are summarized in Table 1. All patients had infiltrated, brown-
Volume 26 Number 3 March 1992
Lupus vulgaris 405
Fig. 1. Clinical appearance of lupus vulgaris affecting the face.
Fig. 2. Tuberculous supraclavicular adenitis (a) in patient with lupus vulgaris on abdominal skin (b).
Table I. Clinical and bacteriologic data of 10 patients Patient
No.
1
Site
2
38jF 54jM
3
24jF
4 5 6
46jF 77jM 49jF 35jF 43jF 63jM 43jM
7 8 9
10
Face Buttocks (multiple) Face, shoulders, thighs Face Trunk Thigh Face Face Face Trunk
Previous tuberculosis
Scrofuloderma
Simultaneous tuberculosis
Abscess (buttocks)
Skin culture
+
+
Pulmonary Scrofuloderma
Adenitis
+ + + + + + +
+ +
+
ND
+
ND, Not done.
red cutaneous plaques with "apple jelly" nodules on diascopy (Fig. 1). The duration ofthe disease ranged from 4 months to 40 years. Only two patients (2 and 3) had multiple lesions. In most patients LV affected the face (Table 1). Five patients had evidence of either previous (patients 1 and 4) or simultaneous
(patients 2,3, and 5) tuberculous foci in other locations. In patient 1, LV developed in a scrofuloderma scar that had been present for 25 years. Patient 2 had a subcutaneous tuberculous abscess on the buttocks that appeared 12 months before typical LV lesions developed in the same area. In patient 5 a right su-
Journal of the American Academy of Dermatology
406 Marcoval et al.
Fig. 3. a, Tuberculoid granuloma with prominent caseation necrosis. h, Sarcoidlike granulomas with patchy distribution. (Hematoxylin-eosin stain; X160.)
praclavicular adenitis developed shortly after LV of the trunk appeared (Fig. 2). The clinical response to antituberculous therapy was satisfactory in all treated cases. However, hyperpigmentation and atropic scarring remained in some patients. Mycobacterium tuberculosis was isolated from cutaneous lesions in five of nine patients in whom cultures were done (Table I). In patient 5 bacilli were also isolated from supraclavicular adenitis. In patient 3 the cutaneous culture was negative but M. tuberculosis was recovered from the sputum.
Histopathologic features The cutaneous biopsy specimen could be evaluated in nine patients. The epidermis was atrophic in four cases and showed a variable degree of irregular hyperplasia in five. In all specimens, the inflammatory reaction was located in the reticular dermis with extension to the underlying fat in two. Three cases showed tuberculoid granulomas with prominent central caseation necrosis and a peripheral coat of lymphocytes (Fig. 3, a). The granulomas were confluent and Langhans giant cells were easily demonstrated. In three cases, the granulomatous reaction was sarcoidlike. Some granulomas were small with a patchy distribution without confluence (Fig. 3, b). In these granulomas, caseation necrosis was absent and the peripheral lymphocytic component was less pronounced. Three cases disclosed a "mixed" pat-
tern with confluent granulomas but no caseation necrosis. Special stains for acid-fast bacilli were negative in all cases in which they were performed. DISCUSSION
LV is a chronic form of cutaneous tuberculosis that arises in persons previously infected elsewhere with M. tuberculosis. In rare instances LV has been reported after primary inoculation or BeG vaccination but contiguous, lymphatic, or hematogenous spread from a tuberculous lesion or clinically inapparent tuberculous focus, has been proposed as the usual pathogenic mechanism. 6,11-13 However, in many cases the exact way in which LV develops is difficult to assess. The clinical findings in our patients suggest that different mechanisms are involved in the development of LV. In patient I, LV developed in a chronic cervical scrofuloderma scar. In patient 2 typical LV plaques developed at the periphery of a subcutaneous tuberculous abscess. These patients probably represent contiguous spread of the infection. Patient 3 had widely distributed, multiple, cutaneous lesions and active pulmonary tuberculosis. Although skin cultures were negative, M. tuberculosis was isolated from the sputum. In this case hematogenous spread of the organism from the lung was the likely cause of LV. Patient 4, with LV on the face, had had cervical
Volume 26 Number 3 March 1992
scrofula in childhood. In patient 5 supraclavicular tuberculous adenitis appeared shortly after a diagnosis of LV ofthe abdominal skin was made. In these cases dissemination to the lymph nodes and skin from an unknown primary focus is the most likely pathogenic mechanism. The remaining five patients had no evidence of either past or active tuberculous infection other than LV. In such cases, reactivation of a latent cutaneous focus secondary to a previous silent bacillemia can be postulated. Although LV is usually regarded as a benign chronic form of cutaneous tuberculosis, simultaneous association with tuberculosis elsewhere has been reported in 9% to 19% of patients. 5, 8, 14 Five of our 10 patients had evidence of a tuberculous infection other than LV. The Mantoux test is positive in most cases of L V3-5 so a negative reaction provides strong evidence against tuberculosis.! However, reactivity to tuberculin may be reduced by conditions that diminish delayed hypersensitivity reactions. In the present study, the two patients who did not react to purified protein derivative had another tuberculous disease and multifocal LV. This suggests that a negative Mantoux test in a patient with LV should be regarded as a sign of possible visceral involvement. Culture can be negative in a significant number of cases of LV. 3,4, 8, 15 In our series culture was frequently positive. Positive cultures were obtained in patients with solitary and multiple lesions, in patients with and without multiple tuberculous foci, and in patients with and without tuberculin sensitivity. Therefore no relation between clinical and bacteriologic findings could be found. Therapy with isoniazid alone has been proposed for LV when the disease is confined to the skin. 6, 7, 13 Patient 6 received two 9-month courses'~f isoniazid; however, each time the drug was discontinued, LV reappeared. Although studies demonstrated sensitivity to· the drug, bacteria could still be cultured from the cutaneous lesions. These findings strongly
Lupus vulgaris 407 suggest that isoniazid alone is not an appropriate treatment for LV. Moreover, the frequency of simultaneous visceral involvement, which can be clinically inapparent, leads us to recommend that LV patients receive the same multiple therapy given to patients with visceral tuberculosis.
REFERENCES 1. Kakakhel KU, Fritsch P. Cutaneous tuberculosis. Int J
Dermatol1989;28:355-62. 2. Orange 1M. Mycobacteria and the skin. Int 1 Dermatol 1982;21:497-503. 3. Ramesh V, Misra RS, lain RK. Secondary tuberculosis of the skin: clinical features and problems in laboratory diagnosis. Int J DermatoI1987;26:578-81. 4. Sehgal VN, Srivastava 0, Khurana VK, et al. An appraisal of epidemiologic, clinical, bacteriologic, histopathologic, and immunologic parameters in cutaneous tuberculosis. Int J DermatolI987;26:521-6. 5. Wong KO, Lee KP, Chiu SF. Tuberculosis of the skin in Hong Kong (a review of 160 cases). Br 1 Dermatol 1968;80:424-9. 6. Sehgal VN, Wagh SA. Cutaneous tuberculosis: current concepts. Int J DermatolI990;29:237-52. 7. Savin JA, Wilkinson DS. Mycobacterial infections including tuberculosis. In: Rook A, Wilkinson DS, Ebling FJG, et aI, eds. Textbook of dermatology. London: Blackwell Scientific Publications, 1986:791-822. 8. HorwitzO. Lupus vulgaris cutis in Denmark 1895-1954: its relation to the epidemiology of other forms of tuberculosis. Acta Tuberc Scand (Suppl) 1960;49:1-122. 9. Forstrom L. Frequency of other types of tuberculosis in patients with tuberculosis oftheskin. Scand 1 Clin Lab Invest (Suppl) 1969;23:1-37. 10. Michelson HE. Criteria for the diagnosis of certain tuberculoderms. lAMA 1948;138:721-6. 11. Wolff K, Tappeiner G. Mycobacterial diseases: tuberculosis and atypical mycobacterial infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. New York: McGraw Hill, 1987:2152-80. 12. Lantos G, Fisher BK, Contreras M. Tuberculous ulcer of the skin. J AM ACAD DERMATOL 1988;19:1067-72. 13. Beyt BE, Ortbals DW, Santa Cruz DJ, et al. Cutaneous mycobacteriosis: analysis of 34 cases with a new classification of the disease. Medicine 1981;60:95-109. 14. Morrison lGL, Fourie ED. The papulonecrotic tuberculide. From Arthus reaction to lupus vulgaris. Br 1 Dermatol 1974;91 :263-70. 15. Van der Lugt L. Some remarks about tuberculosis of the skin and tuberculids. Dennatologica 1965;131:266-75.
Background: Lupus vulgaris (LV) represents the most common form of cutaneous tuberculosis in Europe. However, recent reports from European countries are few and usually limited to isolated cases. Objective: We report the clinical, histopathologic, and bacteriologic data in 10 patients with LV. Methods: The diagnosis of LV was made according to a combination of clinical, histologic, and bacteriologic criteria. In each case a biopsy specimen was obtained for histopathologic study and mycobacteriologic culture. All but one patient received a 9-month course of combined antituberculous therapy. Results: Five patients had evidence of either previous or simultaneous tuberculous foci other than LV. Mycobacterium tuberculosis was isolated from cutaneous lesions in five cases. The histologic study revealed a variable granulomatous reaction, including tuberculoid granulomas, sarcoidlike granulomas, and a "mixed" granulomatous reaction. Conclusion: Although different mechanisms could be implicated in the development of LV, an association with visceral tuberculosis is not infrequent. Combined antituberculous therapy should be the treatment of choice in these patients. (J AM ACAD DERMATOL 1992;26:404-7.) The incidence of cutaneous tuberculosis has been progressively decreasing in industrially developed countries during this century. 1,2 Improved hygiene and living standards as well as antituberculous therapy are responsible for this change. 3 However, infections caused by mycobacteria are still common in some areas. Large series have been reported from Asia3-6 while recent reports from developed countries are usually limited to isolated cases. We examined the records of lO patients with lupus vulgaris (LV), the most common form of cutaneous tuberculosis in Europe.5-10
PATIENTS AND METHODS Ten patients (four men, six women; age ranging from 24 to 77 years) with LVdiagnosed from 1985 to 1990 are included. The diagnosis of LV was made according to a combination of criteria including chronic cutaneous
From the Departments of Dermatology" and Pathology,b Hospital "Princeps D'Espanya." Accepted for publication Sept. 23, 1991. Reprint requests: Joaquim Marcoval, MD, PzTetuan 38-39 II 2,08010 Barcelona, Spain.
16/1/33976
404
plaques with "apple jelly" nodules, an inflammatory granulomatous reaction on histologic examination, microbiologic findings, presence of active tuberculosis elsewhere, the results of the Mantoux test, and response to antituberculous therapy. The Mantoux test was performed in all patients by injecting intradermally 5 TV of commercially available tuberculin. Other routine investigations included complete blood cell count, total and differential leukocyte count, erythrocyte sedimentation rate, and chest roentgenography. In each case a biopsy specimen oflesional skin was obtained. Half the specimen was cultured in LowensteinJensen medium. The other half was formalin-fixed and processed by routine methods. The histologic sections were stained with hematoxylin-eosin and special stains for acid-fast bacilli. All but one patient were treated with a 9-month course of isoniazid (5 to 10 mg/kg/day) and rifampicin (10 to 20 mg/kg/day) supplemented by a 3-month initial phase of ethambutol (15 to 25 mg/kg/day). Patient 5 was also treated by drainage of a supraclavicular adenitis. In patient 1 the lesion was surgically excised as the only form of therapy.
RESULTS
Clinical features The clinical and bacteriologic data are summarized in Table 1. All patients had infiltrated, brown-
Volume 26 Number 3 March 1992
Lupus vulgaris 405
Fig. 1. Clinical appearance of lupus vulgaris affecting the face.
Fig. 2. Tuberculous supraclavicular adenitis (a) in patient with lupus vulgaris on abdominal skin (b).
Table I. Clinical and bacteriologic data of 10 patients Patient
No.
1
Site
2
38jF 54jM
3
24jF
4 5 6
46jF 77jM 49jF 35jF 43jF 63jM 43jM
7 8 9
10
Face Buttocks (multiple) Face, shoulders, thighs Face Trunk Thigh Face Face Face Trunk
Previous tuberculosis
Scrofuloderma
Simultaneous tuberculosis
Abscess (buttocks)
Skin culture
+
+
Pulmonary Scrofuloderma
Adenitis
+ + + + + + +
+ +
+
ND
+
ND, Not done.
red cutaneous plaques with "apple jelly" nodules on diascopy (Fig. 1). The duration ofthe disease ranged from 4 months to 40 years. Only two patients (2 and 3) had multiple lesions. In most patients LV affected the face (Table 1). Five patients had evidence of either previous (patients 1 and 4) or simultaneous
(patients 2,3, and 5) tuberculous foci in other locations. In patient 1, LV developed in a scrofuloderma scar that had been present for 25 years. Patient 2 had a subcutaneous tuberculous abscess on the buttocks that appeared 12 months before typical LV lesions developed in the same area. In patient 5 a right su-
Journal of the American Academy of Dermatology
406 Marcoval et al.
Fig. 3. a, Tuberculoid granuloma with prominent caseation necrosis. h, Sarcoidlike granulomas with patchy distribution. (Hematoxylin-eosin stain; X160.)
praclavicular adenitis developed shortly after LV of the trunk appeared (Fig. 2). The clinical response to antituberculous therapy was satisfactory in all treated cases. However, hyperpigmentation and atropic scarring remained in some patients. Mycobacterium tuberculosis was isolated from cutaneous lesions in five of nine patients in whom cultures were done (Table I). In patient 5 bacilli were also isolated from supraclavicular adenitis. In patient 3 the cutaneous culture was negative but M. tuberculosis was recovered from the sputum.
Histopathologic features The cutaneous biopsy specimen could be evaluated in nine patients. The epidermis was atrophic in four cases and showed a variable degree of irregular hyperplasia in five. In all specimens, the inflammatory reaction was located in the reticular dermis with extension to the underlying fat in two. Three cases showed tuberculoid granulomas with prominent central caseation necrosis and a peripheral coat of lymphocytes (Fig. 3, a). The granulomas were confluent and Langhans giant cells were easily demonstrated. In three cases, the granulomatous reaction was sarcoidlike. Some granulomas were small with a patchy distribution without confluence (Fig. 3, b). In these granulomas, caseation necrosis was absent and the peripheral lymphocytic component was less pronounced. Three cases disclosed a "mixed" pat-
tern with confluent granulomas but no caseation necrosis. Special stains for acid-fast bacilli were negative in all cases in which they were performed. DISCUSSION
LV is a chronic form of cutaneous tuberculosis that arises in persons previously infected elsewhere with M. tuberculosis. In rare instances LV has been reported after primary inoculation or BeG vaccination but contiguous, lymphatic, or hematogenous spread from a tuberculous lesion or clinically inapparent tuberculous focus, has been proposed as the usual pathogenic mechanism. 6,11-13 However, in many cases the exact way in which LV develops is difficult to assess. The clinical findings in our patients suggest that different mechanisms are involved in the development of LV. In patient I, LV developed in a chronic cervical scrofuloderma scar. In patient 2 typical LV plaques developed at the periphery of a subcutaneous tuberculous abscess. These patients probably represent contiguous spread of the infection. Patient 3 had widely distributed, multiple, cutaneous lesions and active pulmonary tuberculosis. Although skin cultures were negative, M. tuberculosis was isolated from the sputum. In this case hematogenous spread of the organism from the lung was the likely cause of LV. Patient 4, with LV on the face, had had cervical
Volume 26 Number 3 March 1992
scrofula in childhood. In patient 5 supraclavicular tuberculous adenitis appeared shortly after a diagnosis of LV ofthe abdominal skin was made. In these cases dissemination to the lymph nodes and skin from an unknown primary focus is the most likely pathogenic mechanism. The remaining five patients had no evidence of either past or active tuberculous infection other than LV. In such cases, reactivation of a latent cutaneous focus secondary to a previous silent bacillemia can be postulated. Although LV is usually regarded as a benign chronic form of cutaneous tuberculosis, simultaneous association with tuberculosis elsewhere has been reported in 9% to 19% of patients. 5, 8, 14 Five of our 10 patients had evidence of a tuberculous infection other than LV. The Mantoux test is positive in most cases of L V3-5 so a negative reaction provides strong evidence against tuberculosis.! However, reactivity to tuberculin may be reduced by conditions that diminish delayed hypersensitivity reactions. In the present study, the two patients who did not react to purified protein derivative had another tuberculous disease and multifocal LV. This suggests that a negative Mantoux test in a patient with LV should be regarded as a sign of possible visceral involvement. Culture can be negative in a significant number of cases of LV. 3,4, 8, 15 In our series culture was frequently positive. Positive cultures were obtained in patients with solitary and multiple lesions, in patients with and without multiple tuberculous foci, and in patients with and without tuberculin sensitivity. Therefore no relation between clinical and bacteriologic findings could be found. Therapy with isoniazid alone has been proposed for LV when the disease is confined to the skin. 6, 7, 13 Patient 6 received two 9-month courses'~f isoniazid; however, each time the drug was discontinued, LV reappeared. Although studies demonstrated sensitivity to· the drug, bacteria could still be cultured from the cutaneous lesions. These findings strongly
Lupus vulgaris 407 suggest that isoniazid alone is not an appropriate treatment for LV. Moreover, the frequency of simultaneous visceral involvement, which can be clinically inapparent, leads us to recommend that LV patients receive the same multiple therapy given to patients with visceral tuberculosis.
REFERENCES 1. Kakakhel KU, Fritsch P. Cutaneous tuberculosis. Int J
Dermatol1989;28:355-62. 2. Orange 1M. Mycobacteria and the skin. Int 1 Dermatol 1982;21:497-503. 3. Ramesh V, Misra RS, lain RK. Secondary tuberculosis of the skin: clinical features and problems in laboratory diagnosis. Int J DermatoI1987;26:578-81. 4. Sehgal VN, Srivastava 0, Khurana VK, et al. An appraisal of epidemiologic, clinical, bacteriologic, histopathologic, and immunologic parameters in cutaneous tuberculosis. Int J DermatolI987;26:521-6. 5. Wong KO, Lee KP, Chiu SF. Tuberculosis of the skin in Hong Kong (a review of 160 cases). Br 1 Dermatol 1968;80:424-9. 6. Sehgal VN, Wagh SA. Cutaneous tuberculosis: current concepts. Int J DermatolI990;29:237-52. 7. Savin JA, Wilkinson DS. Mycobacterial infections including tuberculosis. In: Rook A, Wilkinson DS, Ebling FJG, et aI, eds. Textbook of dermatology. London: Blackwell Scientific Publications, 1986:791-822. 8. HorwitzO. Lupus vulgaris cutis in Denmark 1895-1954: its relation to the epidemiology of other forms of tuberculosis. Acta Tuberc Scand (Suppl) 1960;49:1-122. 9. Forstrom L. Frequency of other types of tuberculosis in patients with tuberculosis oftheskin. Scand 1 Clin Lab Invest (Suppl) 1969;23:1-37. 10. Michelson HE. Criteria for the diagnosis of certain tuberculoderms. lAMA 1948;138:721-6. 11. Wolff K, Tappeiner G. Mycobacterial diseases: tuberculosis and atypical mycobacterial infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. New York: McGraw Hill, 1987:2152-80. 12. Lantos G, Fisher BK, Contreras M. Tuberculous ulcer of the skin. J AM ACAD DERMATOL 1988;19:1067-72. 13. Beyt BE, Ortbals DW, Santa Cruz DJ, et al. Cutaneous mycobacteriosis: analysis of 34 cases with a new classification of the disease. Medicine 1981;60:95-109. 14. Morrison lGL, Fourie ED. The papulonecrotic tuberculide. From Arthus reaction to lupus vulgaris. Br 1 Dermatol 1974;91 :263-70. 15. Van der Lugt L. Some remarks about tuberculosis of the skin and tuberculids. Dennatologica 1965;131:266-75.