308
Tubercle and Lung Disease
hyperplasia of glomeruli. Immunofluorescent study presented positive IgM stain (++) with granular pattern. Skin biopsy specimens also showed lymphocytic vasculitis. Liver echogram revealed hepatomegaly with 18 cm liver span. All antituberculosis drugs were withdrawn, and the patient’s condition improved gradually. Progressive improvement in her cutaneous vasculitis lesions and renal function were also noted. Simultaneously there was resolution of the abnormalities of hepatitic function. She was discharged with complete recovery on hospital day 21. At the outpatient department, isoniazid 300 mg and ethambutol 1200 mg were reintroduced because her pulmonary condition had deteriorated. Two weeks after isoniazid and ethambutol rechallenge, she developed generalized erythema with desquamation, spiking high fever, and eosinophilia again. Exofoliative dermatosis without cutaneous vasculitis lesions was also noted in the latter. Laboratory data showed normal liver and renal function. No hepatomegaly and lymphadenopathy were found. Isoniazid and ethambutol were ceased again and short-term steroid therapy was commenced. The skin lesions and high fever subsided rapidly. Finally, ethambutol 1200 mg and streptomycin 0.75 g per day were reintroduced. However, the patient’s pulmonary condition continued to improve. No toxic effects of the treatment regimen have occurred till now. There seems little doubt that this patient’s cutaneous vasculitis, acute renal failure and hepatitis were related to rifampicin therapy. These manifestations did not occur after isoniazid and ethambutol were reintroduced. The withdrawal of isoniazid and treatment with ethambutol and streptomycin caused the smooth therapeutic course of this case. The most common pathological abnormalities of rifampicin-induced renal failure are renal tubule necrosis, interstitial nephritis and tubule fibrosis, and glomerular lesions are very uncommon.“’ Our patient’s renal biopsy showed renal tubule necrosis and glomerular mesangial hyperplasia with granular IgM deposition. Although the main component of anti-rifampicin antibodies is IgM, the relation between antibodies and renal failure is still unknown.3 Allergic cutaneous vasculitis rarely occurs in patients with rifampicin therapy. There is only one report, from Iredale et al! They described cutaneous vasculitis related to rifampicin, but did not perform further pathological studies in their case. Our case is probably the first to demonstrate rifampicin-induced lymphocytic vasculitis. The vasculitis was only limited to the skin, as there was not the same lesion in our renal biopsy specimens. This is why the rapid resolution of cutaneous vasculitis after withdrawal of the drugs and the more benign clinical course of our patient were noted.5 Ja-Liang Lin Sau-An Hu Poison Center Division of Nephrology Chang Gung Memorial Hospital Taipei, Taiwan
References 1. Grosset J, Leventis S. Adverse effects of rifampicin. Rev Infect Dis
1983; 5 (suppl3): S440-446. 2. Cohn J R, Fye D L, Sillis J M, Frances G C. Rifampicin-induced renal failure. Tubercle 1985; 66: 289-293. 3. Mauri J M, Fort J, Bartolome J, Camps J, Capdevila L, Morlans M et al. Antirifampicin antibodies in acute rifampin-associated renal failure. Nephron 1982; 31: 177-179. 4. DeSwarte R D. Drug allergy-problem and strategies. J Allergy Clin Immunol 1984; 74: 209-22 1. 5. Winkelmann R K, Ditto W B. Cutaneous and visceral syndromes of necrotizing or ‘allergic’ angitis. A study of 38 cases. J Invest Dermatol 1964; 43: 59-89.
Adenosine deaminase levels in cerebrospinal @id in tuberculosis and bacterial meningitis We have read the article of Chawla et al’ on the subject of adenosine deaminase (ADA) levels in cerebrospinal fluid (CSF) with interest and concern. Interest because we concur with their results, but concern because our published work on the subject has been misquoted.2 We did not claim that ADA levels in the CSF were ‘useful in distinguishing TBM from bacterial meningitis’. The summary of our first study states: ‘It (CSF, ADA levels) could not distinguish bacterial meningitis from tuberculous or aseptic meningitis. In cases of low cell count bacterial meningitis, the mean cerebrospinal fluid adenosine deaminase level was significantly lower than in cases of tuberculous meningitis with a similar cell count, but considerable overlap of results in the two groups was still to be found’. Our subsequent published experience3 confirmed the above opinion, as does the work of Chawla et al, and we are now reasonably sure that ADA activity in the CSF will in most cases of meningitis reflect increased permeability of the blood-brain barrier and will show a close relationship to increases in the CSF protein.4 Professor P. R. Donald Department
of Paediatrics and Child Health University of Stellenbosch P 0 Box 19063 Tygerberg 7.505 South Africa
References Chawla R K, Seth R K, Raj B, Saini A D. Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis. Tubercle 1991; 72: 190-192. Malan C, Donald P R, Golden M, Taljaard J J F Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculosis meningitis. J Trop Med Hyg 1984; 87: 33-40. Donald P R, Malan C, Van der Walt A, Schoeman J F. The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. S Afr Med J 1986; 69: 505-507. Donald P R, Malan C, Schoeman J F. Adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. J Infect Dis 1987; 156: 104~1041.
The above letter was referred to the authors of the article in question, who offer the following reply:
I have read the above letter from Dr Donald. Our results are in agreement with his results of ADA in tuberculosis
Correspondence 309 and bacterial meningitis. However, if by mistake they have been misquoted by any of the authors/co-authors of this paper the error is regretted. Dr R. K. Seth Associate professor Biochemistry Medical College 28/9J Medical Enclave Rohtak 124001, Haryana India
Proposal of an improved score method for the diagnosis of pulmonary tuberculosis I was interested
to read the article by G. B. Migliori et al,’ which proposes to facilitate the diagnosis of pulmonary tuberculosis in children under the age of 5 in developing countries by applying a new simplified score method. The interest of the proposed method would be to be able to apply it in current practice where X-ray and laboratory facilities are not available. The authors correctly insist on the specificity of microscopical examinations of samples collected after gastric lavage, even though this method is not easy to apply to young children outside a district hospital. However, aside from this indisputable diagnostic criterion, the authors propose to retain as another diagnostic criterion the ‘response to tuberculosis treatment’ (RTT) which seems to me to be inappropriate and certainly debatable. In fact, the signs proposed to define this criterion (weight gain, disappearance of respiratory symptoms) are not specific: they could also just as easily be observed in children under 5 with acute respiratory infection (viral or bacterial), nourished under the same conditions, especially if at the same time they are
receiving treatment with antibacterial drugs not specific to tuberculosis (such as streptomycin or rifampicin). It would be interesting to examine the, merit of this criterion in a control group of non-tuberculous chifdren. But my main criticism is that the proposed method (like all other ‘score’ methods) should aim at aiding a precise diagnosis before the prescription of a specific antituberculosis treatment, and not at confirming the diagnosis 2 or 4 months later by the apparent ‘success’ of the antituberculosis treatment. The fact that the ‘response to tuberculosis treatment’ criteria appeared sensitive and specific in a selected group of young children because they were suspected of having tuberculosis is not in itseIf paradoxical. This is why it seems to me an exaggeration to recommend in the technical guidelines for national antituberculosis programmes in developing countries the ‘response to tuberculosis treatment’ as a diagnostic criterion for pulmonary tuberculosis in children under 5 years of age. This attitude could well create a certain amount of confusion in the minds of the medical personnel responsible for establishing the diagnosis of pulmonary tuberculosis and other respiratory infections in children, as well as raising the number of nontuberculosis children submitted unnecessarily to a ‘test’ antituberculosis treatment. F’rofesseur Pierre Chaulet Unique de Pneumo-Phtisiologie A4atiben H6pital de Beni-Messous Centre Hospitalier Universitaire d’Alger-Ouest Alger, Algerie
Reference 1.
Migliori G.B., BorghesiA, RossanigoP et al. Proposalof an improved score methodfor the diagnosis of pulmonary tuberculosis.There Lung Dis 1992: 73; 145-149.
Tubercle and Lung Disease
hyperplasia of glomeruli. Immunofluorescent study presented positive IgM stain (++) with granular pattern. Skin biopsy specimens also showed lymphocytic vasculitis. Liver echogram revealed hepatomegaly with 18 cm liver span. All antituberculosis drugs were withdrawn, and the patient’s condition improved gradually. Progressive improvement in her cutaneous vasculitis lesions and renal function were also noted. Simultaneously there was resolution of the abnormalities of hepatitic function. She was discharged with complete recovery on hospital day 21. At the outpatient department, isoniazid 300 mg and ethambutol 1200 mg were reintroduced because her pulmonary condition had deteriorated. Two weeks after isoniazid and ethambutol rechallenge, she developed generalized erythema with desquamation, spiking high fever, and eosinophilia again. Exofoliative dermatosis without cutaneous vasculitis lesions was also noted in the latter. Laboratory data showed normal liver and renal function. No hepatomegaly and lymphadenopathy were found. Isoniazid and ethambutol were ceased again and short-term steroid therapy was commenced. The skin lesions and high fever subsided rapidly. Finally, ethambutol 1200 mg and streptomycin 0.75 g per day were reintroduced. However, the patient’s pulmonary condition continued to improve. No toxic effects of the treatment regimen have occurred till now. There seems little doubt that this patient’s cutaneous vasculitis, acute renal failure and hepatitis were related to rifampicin therapy. These manifestations did not occur after isoniazid and ethambutol were reintroduced. The withdrawal of isoniazid and treatment with ethambutol and streptomycin caused the smooth therapeutic course of this case. The most common pathological abnormalities of rifampicin-induced renal failure are renal tubule necrosis, interstitial nephritis and tubule fibrosis, and glomerular lesions are very uncommon.“’ Our patient’s renal biopsy showed renal tubule necrosis and glomerular mesangial hyperplasia with granular IgM deposition. Although the main component of anti-rifampicin antibodies is IgM, the relation between antibodies and renal failure is still unknown.3 Allergic cutaneous vasculitis rarely occurs in patients with rifampicin therapy. There is only one report, from Iredale et al! They described cutaneous vasculitis related to rifampicin, but did not perform further pathological studies in their case. Our case is probably the first to demonstrate rifampicin-induced lymphocytic vasculitis. The vasculitis was only limited to the skin, as there was not the same lesion in our renal biopsy specimens. This is why the rapid resolution of cutaneous vasculitis after withdrawal of the drugs and the more benign clinical course of our patient were noted.5 Ja-Liang Lin Sau-An Hu Poison Center Division of Nephrology Chang Gung Memorial Hospital Taipei, Taiwan
References 1. Grosset J, Leventis S. Adverse effects of rifampicin. Rev Infect Dis
1983; 5 (suppl3): S440-446. 2. Cohn J R, Fye D L, Sillis J M, Frances G C. Rifampicin-induced renal failure. Tubercle 1985; 66: 289-293. 3. Mauri J M, Fort J, Bartolome J, Camps J, Capdevila L, Morlans M et al. Antirifampicin antibodies in acute rifampin-associated renal failure. Nephron 1982; 31: 177-179. 4. DeSwarte R D. Drug allergy-problem and strategies. J Allergy Clin Immunol 1984; 74: 209-22 1. 5. Winkelmann R K, Ditto W B. Cutaneous and visceral syndromes of necrotizing or ‘allergic’ angitis. A study of 38 cases. J Invest Dermatol 1964; 43: 59-89.
Adenosine deaminase levels in cerebrospinal @id in tuberculosis and bacterial meningitis We have read the article of Chawla et al’ on the subject of adenosine deaminase (ADA) levels in cerebrospinal fluid (CSF) with interest and concern. Interest because we concur with their results, but concern because our published work on the subject has been misquoted.2 We did not claim that ADA levels in the CSF were ‘useful in distinguishing TBM from bacterial meningitis’. The summary of our first study states: ‘It (CSF, ADA levels) could not distinguish bacterial meningitis from tuberculous or aseptic meningitis. In cases of low cell count bacterial meningitis, the mean cerebrospinal fluid adenosine deaminase level was significantly lower than in cases of tuberculous meningitis with a similar cell count, but considerable overlap of results in the two groups was still to be found’. Our subsequent published experience3 confirmed the above opinion, as does the work of Chawla et al, and we are now reasonably sure that ADA activity in the CSF will in most cases of meningitis reflect increased permeability of the blood-brain barrier and will show a close relationship to increases in the CSF protein.4 Professor P. R. Donald Department
of Paediatrics and Child Health University of Stellenbosch P 0 Box 19063 Tygerberg 7.505 South Africa
References Chawla R K, Seth R K, Raj B, Saini A D. Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis. Tubercle 1991; 72: 190-192. Malan C, Donald P R, Golden M, Taljaard J J F Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculosis meningitis. J Trop Med Hyg 1984; 87: 33-40. Donald P R, Malan C, Van der Walt A, Schoeman J F. The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. S Afr Med J 1986; 69: 505-507. Donald P R, Malan C, Schoeman J F. Adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. J Infect Dis 1987; 156: 104~1041.
The above letter was referred to the authors of the article in question, who offer the following reply:
I have read the above letter from Dr Donald. Our results are in agreement with his results of ADA in tuberculosis
Correspondence 309 and bacterial meningitis. However, if by mistake they have been misquoted by any of the authors/co-authors of this paper the error is regretted. Dr R. K. Seth Associate professor Biochemistry Medical College 28/9J Medical Enclave Rohtak 124001, Haryana India
Proposal of an improved score method for the diagnosis of pulmonary tuberculosis I was interested
to read the article by G. B. Migliori et al,’ which proposes to facilitate the diagnosis of pulmonary tuberculosis in children under the age of 5 in developing countries by applying a new simplified score method. The interest of the proposed method would be to be able to apply it in current practice where X-ray and laboratory facilities are not available. The authors correctly insist on the specificity of microscopical examinations of samples collected after gastric lavage, even though this method is not easy to apply to young children outside a district hospital. However, aside from this indisputable diagnostic criterion, the authors propose to retain as another diagnostic criterion the ‘response to tuberculosis treatment’ (RTT) which seems to me to be inappropriate and certainly debatable. In fact, the signs proposed to define this criterion (weight gain, disappearance of respiratory symptoms) are not specific: they could also just as easily be observed in children under 5 with acute respiratory infection (viral or bacterial), nourished under the same conditions, especially if at the same time they are
receiving treatment with antibacterial drugs not specific to tuberculosis (such as streptomycin or rifampicin). It would be interesting to examine the, merit of this criterion in a control group of non-tuberculous chifdren. But my main criticism is that the proposed method (like all other ‘score’ methods) should aim at aiding a precise diagnosis before the prescription of a specific antituberculosis treatment, and not at confirming the diagnosis 2 or 4 months later by the apparent ‘success’ of the antituberculosis treatment. The fact that the ‘response to tuberculosis treatment’ criteria appeared sensitive and specific in a selected group of young children because they were suspected of having tuberculosis is not in itseIf paradoxical. This is why it seems to me an exaggeration to recommend in the technical guidelines for national antituberculosis programmes in developing countries the ‘response to tuberculosis treatment’ as a diagnostic criterion for pulmonary tuberculosis in children under 5 years of age. This attitude could well create a certain amount of confusion in the minds of the medical personnel responsible for establishing the diagnosis of pulmonary tuberculosis and other respiratory infections in children, as well as raising the number of nontuberculosis children submitted unnecessarily to a ‘test’ antituberculosis treatment. F’rofesseur Pierre Chaulet Unique de Pneumo-Phtisiologie A4atiben H6pital de Beni-Messous Centre Hospitalier Universitaire d’Alger-Ouest Alger, Algerie
Reference 1.
Migliori G.B., BorghesiA, RossanigoP et al. Proposalof an improved score methodfor the diagnosis of pulmonary tuberculosis.There Lung Dis 1992: 73; 145-149.
