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Angioneurotic oedema following ingestion of paracetamol
This work was carried out during the author’s assignment to Vanuatu as a United Nations Volunteer within the UN Development Programme. NADiR PAKSOY District Norsup,
Medical Malekula
Officer, Island,
Vanuatu
address: Turkn’.
Cami
Erkan
*Present Istanbul,
Sok,
Apt
16!14
Kucukyalz,
References S. & Schepens, J. (1985). Malaria control programme of Vanuatu in 1984. Ministry of Health, Port Vila, Vanuatu. Macgregor, J. D. & Avery, J. G. (1974). Malaria transmission and fetal growth (Solomon Islands). British Medical Journal, iii, 433-436. McGregor, I. A., Wilson, M. E. & Billewicz, W. Z. (1983). Malaria infection of the placenta in the Gambia, West Africa; its incidence and relationship to stillbirth and placental weight. Transactions of the Royal Sociecv of Tropxal Medicme & Hygiene, 7’7, 232-244. Ratard, R. C. (1979). Epidemiology of malaria in the New Hebrides. Tropcuzl Doctor, 9, 212-216. Taufa, T. (1978). Malaria and pregnancy. Papua .v
Ahn,
Accepted
for publication
A&one&tic
12th June,
1985.
oedema following ingestion of paracetamol The case of a 35year-old soldier who developed a severe angioneurotic oedema following self medication with paracetamol, a commonly prescribed drug, is described. This is a very rare adverse reaction to this drug. The patient was well until the day before his admission when he took two 500mg tablets of paracetamol for a mild headache. Within three hours of taking the tablets, he noticed fever and by about six hours he had observed that his tongue and both lips were becoming swollen. His tongue had filled his mouth and was protruding out of it. 12 hours later, he was rushed to the Ahmadu Bello University Hospital, Zaria, because the swellings had progressed to his face, eye and neck, and he had become very short of breath. He had taken paracetamol four and six years earlier and each time had noticed areas of Iixed drug eruption and consequently he had avoided paracetamol and its compounds until this occasion, He was not asthmatic and there was no family history of allergic disorders. Physical examination revealed his heart rate was 1OOimin and regular, Bn was 120/180 and temnerature was 39°C. He was very hyspnoeic and cyanosed with a resoiratorv rate of 2Ymin. The whole of his face. eves and upper and lower lips were swollen. His ton&e was grossly oedematous-and was protruding fromthe floor of the mouth which was also swollen. There were three circumscribed areas of fixed drug eruptions distributed over the left upper chest, the left scalpular region and medial aspect of the left thigh. Apart from a few crepitations at the right base of the lungs the rest of the physical examination was unremarkable.
Laboratory investigations showed a haematocrit of 38%. The WBC was 6.3 x lo911 with 70% neutrophils, 1% eosinophils, 27% lymphocytes and 2% monocytes. Urine analysis, liver functions tests, urea and electrolytes were all normal and blood cultures were negative. The chest X-ray showed patchy infiltrates in the right lower zone. The levels of serum IgG, IgA and IgM and complement Cs were normal. A diagnosis of angioneurotic oedema secondary to paracetamol ingestion was made. The initial management included the insertion of an airway, intravenous fluids, intravenous hydrocortisone (500mg) which was repeated eight-hourly and parenteral promethazine. Regression of his swollen tongue was noted within four hours of this therapy. By the next day, he was much improved, his facial swelling and oedema of the lips and tongue had considerably subsided. He was therefore, started on oral prednisolone instead of parenteral hydrocortisone and this was subsequently tapered off over seven days as the condition of the patient improved. He was subsequently discharged and was well at follow-up a month later. Paracetamol, a weak inhibitor of prostaglandin production, has been observed very rarely to cause angioneurotic oedema in sensitive individuals including asthmatics (SZCZEKLIK et al., 1977). The underlying pathogenic factors are not well understood. Immunological mechanisms were initially suggested but extensive investigations have failed to support this claim (SPECTOR & FARR, 1983). Clinical observations, coupled with challenge tests have suggested that paracetamol-induced angioedema is not immunomodulated but is due to suppression of prostaglandin production in the tissues of the patient (SZCZEKLIK et al.. 1977). Recent evidence (ASAD et al., 1984) has also confirmed a fall in‘ plasma prostaglandin F 2cu levels following challenge, in aspirin-sensitive patients, a related non-steroidal analgesic drug (NSAIDs). Why there is such individual variation in tolerance to NSAIDs is unknown. The reasons why our patient did not show reaction to the host of other readily available alternative NSAIDs is also not easily understood. We hope this communication will stimulate awareness of the possibility of such a diagnosis in this part of the world and we advocate taking a careful historv of drug allergy, to paracetamol and other NSAIDs in patients with urticaria, angioneurotic oedema and in asthmatic subjects with exacerbations. J. A. IDOKO I. f;uyEPA.ti d. 0: ,\DESAVyA Dept. of Medicine, Ahmadu Belle University Hospital, Zaria, Nigeria. Asad, S. I., Kemeny, D. M. Youlten, L. J. F., Frankland, A. W. & Lessof, M. H. (1984). Effect of aspirin in “aspirin sensitive” patients. British MedicalJournal, 288, 745-748. Spector, S. I. & Farr, R. S. (1983). Aspirin idiosyncracy, asthma and urticaria. In: Allergy: Principles and Practice. (2nd edit.). Middleton, E., Reed, C. E. & Ellis, T. F. (Editors). St. Louis: C. V. Mosby, pp. 1249-1273.
176
TRANSACTIONS OF THE ROYAL SOCIETYOF TROPICALMEDICINEAND HYGIENE(1986), 80. CORRESPONDENCE
Szczeklik, A., Gryglewski, R. J. & Czerwiawska-Mysik, G. (1977). Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. Journal of Allergy and Clinical Immunology, 60, 276-284.
treatment. No hepaticalterationwasobservedandthe biochemicalstandardsstudied remainedat normal levels. Clinical follow-up of the lesions during the course of the treatment showed that the lesions remained
unchangedin five patients,wereaggravatedin six and Accepted fm publication
12th July,
1985.
Failure to cure Leishmania braziliensis guyanensis cutaneous leishmaniasiswith oral ketoconazole Following the report of successfultreatment of Leishmania
nmjor cutaneous
leishmaniasis
by using
400mg daily dosesof ketoconazoleduring 28 days (WEINRAUCH et al.. 1983. 19841,we usedthe same protocol for patients infected ‘&ith L. braziliensis guyanensis.
12adult patients(11 males,onefemale,meanage: 27.6 + 6.3 years)with active cutaneouslesions(total of 29lesions)parasitologicallyconfirmed,participated in the trial. 10 patientshad acquiredtheir infection in French Guiana and two in Suriname. 11 were primarily infected untreated patients (mean duration of the lesions:5.1 f 2.7 weeks)andonewasa relapsingcase eight monthsafter specifictreatment (Pentamidine). They were all informed about the experimental characterof the study and volunteeredto participate. Before, during, and at the end of ketoconazole treatment, bilirubins, seric aminotransferases (ALAT, ASAT), alkaline phosphataseand serum proteinsweredoneto assess hepaticfunction, and the lesionswere searchedfor parasites. The meandiameterof smearamastigotes,development in culture and behaviourin hamsterwere in 11 casescompatible with L. brazilensis complex parasites, and in one casewith L. mexicana complex. Accdrding to the situation of leishmaniasis in French Guiana(DEDET et al.. 19851we assumethat all cases except onewere due to L. 6. guyanensis. The isolates of six casesare maintained in culture and mass cultivation is in progress for further isoenzyme identification. The treatment consistedin a 400 mg (two tablets) daily oral doseof ketoconazoleduring 30 days. When the lesionsweresuperinfected(six cases),the patients were also treated with antibiotics. The treatment was well tolerated and compatible with normal professionaland life activities. Minor
improved in only one case. Three patients developed new lesions during the course of treatment. By the end of the treatment, no clinical cure was observed and eight patients had lesionsstill harbouring para-
sites (positive smears). One month after the end of the treatment, a single patient was clinically cured and in a second patient the first lesion was cured but a second lesion was still
parasitized.A third patient wascured by the second month
following
the end of the treatment.
A second protocol of oral ketoconazole, using double dose (800 mg daily during 30 days), is in progress. We thank Janssen Pharmaceutics for providing us with the ketoconazole and the following medical doctors for providing us with the patients: M. Burlat, F. Lallemand, J. Michaudel, I. Ogorzelski and L. Salinier. JEAN-PIERRE DEDET PIERRE JAMET PHILIPPE ESTERRE PAUL MARIE GHIPPONI CLAUDE GENIN GERARD LALANDE Institut Pasteur de Guyane, Fraqaise, 97306 Cayenne Cedex, French Guiana. References
Dedet, J. P., Pradinaud, R., Desjeux, I’., Jacquet-Viallet, P., Girardeau, I., Esterre P. & GGtz, W. (1985). Deux nremiers cas de leishmaniose cutanCe & Leishmania keiicana amazonensis en Guyane fran@e. Bulletin de la Socild
de l’athologie
exotique,
78, 64-70.
Weinrauch, L., Livshin, R., Even-Paz, Z. & El-On, J. (1983). Efficacy of ketoconazole in cutaneous leishmaniasis. Archives of Dermatological Research, 215, 353354. Weinrauch, L., Livshin, R. & El-On. J. (1984). Comparative study of the efficacy of ketoconazole and rifampicin in the treatment of cutaneous leishmaniasis. Proceedings of the’ Fourth European Multicolloquium of Parasitology, Z.&r, 69-70.
side effects were seen in nine patients (asthenia-six,
sleepiness-two,
pain-two)
without
nervousness-two, necessitating
epigastric
interruption
of the
Accepted for publication
13th August, 1985.
Medical Malekula
Officer, Island,
Vanuatu
address: Turkn’.
Cami
Erkan
*Present Istanbul,
Sok,
Apt
16!14
Kucukyalz,
References S. & Schepens, J. (1985). Malaria control programme of Vanuatu in 1984. Ministry of Health, Port Vila, Vanuatu. Macgregor, J. D. & Avery, J. G. (1974). Malaria transmission and fetal growth (Solomon Islands). British Medical Journal, iii, 433-436. McGregor, I. A., Wilson, M. E. & Billewicz, W. Z. (1983). Malaria infection of the placenta in the Gambia, West Africa; its incidence and relationship to stillbirth and placental weight. Transactions of the Royal Sociecv of Tropxal Medicme & Hygiene, 7’7, 232-244. Ratard, R. C. (1979). Epidemiology of malaria in the New Hebrides. Tropcuzl Doctor, 9, 212-216. Taufa, T. (1978). Malaria and pregnancy. Papua .v
Ahn,
Accepted
for publication
A&one&tic
12th June,
1985.
oedema following ingestion of paracetamol The case of a 35year-old soldier who developed a severe angioneurotic oedema following self medication with paracetamol, a commonly prescribed drug, is described. This is a very rare adverse reaction to this drug. The patient was well until the day before his admission when he took two 500mg tablets of paracetamol for a mild headache. Within three hours of taking the tablets, he noticed fever and by about six hours he had observed that his tongue and both lips were becoming swollen. His tongue had filled his mouth and was protruding out of it. 12 hours later, he was rushed to the Ahmadu Bello University Hospital, Zaria, because the swellings had progressed to his face, eye and neck, and he had become very short of breath. He had taken paracetamol four and six years earlier and each time had noticed areas of Iixed drug eruption and consequently he had avoided paracetamol and its compounds until this occasion, He was not asthmatic and there was no family history of allergic disorders. Physical examination revealed his heart rate was 1OOimin and regular, Bn was 120/180 and temnerature was 39°C. He was very hyspnoeic and cyanosed with a resoiratorv rate of 2Ymin. The whole of his face. eves and upper and lower lips were swollen. His ton&e was grossly oedematous-and was protruding fromthe floor of the mouth which was also swollen. There were three circumscribed areas of fixed drug eruptions distributed over the left upper chest, the left scalpular region and medial aspect of the left thigh. Apart from a few crepitations at the right base of the lungs the rest of the physical examination was unremarkable.
Laboratory investigations showed a haematocrit of 38%. The WBC was 6.3 x lo911 with 70% neutrophils, 1% eosinophils, 27% lymphocytes and 2% monocytes. Urine analysis, liver functions tests, urea and electrolytes were all normal and blood cultures were negative. The chest X-ray showed patchy infiltrates in the right lower zone. The levels of serum IgG, IgA and IgM and complement Cs were normal. A diagnosis of angioneurotic oedema secondary to paracetamol ingestion was made. The initial management included the insertion of an airway, intravenous fluids, intravenous hydrocortisone (500mg) which was repeated eight-hourly and parenteral promethazine. Regression of his swollen tongue was noted within four hours of this therapy. By the next day, he was much improved, his facial swelling and oedema of the lips and tongue had considerably subsided. He was therefore, started on oral prednisolone instead of parenteral hydrocortisone and this was subsequently tapered off over seven days as the condition of the patient improved. He was subsequently discharged and was well at follow-up a month later. Paracetamol, a weak inhibitor of prostaglandin production, has been observed very rarely to cause angioneurotic oedema in sensitive individuals including asthmatics (SZCZEKLIK et al., 1977). The underlying pathogenic factors are not well understood. Immunological mechanisms were initially suggested but extensive investigations have failed to support this claim (SPECTOR & FARR, 1983). Clinical observations, coupled with challenge tests have suggested that paracetamol-induced angioedema is not immunomodulated but is due to suppression of prostaglandin production in the tissues of the patient (SZCZEKLIK et al.. 1977). Recent evidence (ASAD et al., 1984) has also confirmed a fall in‘ plasma prostaglandin F 2cu levels following challenge, in aspirin-sensitive patients, a related non-steroidal analgesic drug (NSAIDs). Why there is such individual variation in tolerance to NSAIDs is unknown. The reasons why our patient did not show reaction to the host of other readily available alternative NSAIDs is also not easily understood. We hope this communication will stimulate awareness of the possibility of such a diagnosis in this part of the world and we advocate taking a careful historv of drug allergy, to paracetamol and other NSAIDs in patients with urticaria, angioneurotic oedema and in asthmatic subjects with exacerbations. J. A. IDOKO I. f;uyEPA.ti d. 0: ,\DESAVyA Dept. of Medicine, Ahmadu Belle University Hospital, Zaria, Nigeria. Asad, S. I., Kemeny, D. M. Youlten, L. J. F., Frankland, A. W. & Lessof, M. H. (1984). Effect of aspirin in “aspirin sensitive” patients. British MedicalJournal, 288, 745-748. Spector, S. I. & Farr, R. S. (1983). Aspirin idiosyncracy, asthma and urticaria. In: Allergy: Principles and Practice. (2nd edit.). Middleton, E., Reed, C. E. & Ellis, T. F. (Editors). St. Louis: C. V. Mosby, pp. 1249-1273.
176
TRANSACTIONS OF THE ROYAL SOCIETYOF TROPICALMEDICINEAND HYGIENE(1986), 80. CORRESPONDENCE
Szczeklik, A., Gryglewski, R. J. & Czerwiawska-Mysik, G. (1977). Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. Journal of Allergy and Clinical Immunology, 60, 276-284.
treatment. No hepaticalterationwasobservedandthe biochemicalstandardsstudied remainedat normal levels. Clinical follow-up of the lesions during the course of the treatment showed that the lesions remained
unchangedin five patients,wereaggravatedin six and Accepted fm publication
12th July,
1985.
Failure to cure Leishmania braziliensis guyanensis cutaneous leishmaniasiswith oral ketoconazole Following the report of successfultreatment of Leishmania
nmjor cutaneous
leishmaniasis
by using
400mg daily dosesof ketoconazoleduring 28 days (WEINRAUCH et al.. 1983. 19841,we usedthe same protocol for patients infected ‘&ith L. braziliensis guyanensis.
12adult patients(11 males,onefemale,meanage: 27.6 + 6.3 years)with active cutaneouslesions(total of 29lesions)parasitologicallyconfirmed,participated in the trial. 10 patientshad acquiredtheir infection in French Guiana and two in Suriname. 11 were primarily infected untreated patients (mean duration of the lesions:5.1 f 2.7 weeks)andonewasa relapsingcase eight monthsafter specifictreatment (Pentamidine). They were all informed about the experimental characterof the study and volunteeredto participate. Before, during, and at the end of ketoconazole treatment, bilirubins, seric aminotransferases (ALAT, ASAT), alkaline phosphataseand serum proteinsweredoneto assess hepaticfunction, and the lesionswere searchedfor parasites. The meandiameterof smearamastigotes,development in culture and behaviourin hamsterwere in 11 casescompatible with L. brazilensis complex parasites, and in one casewith L. mexicana complex. Accdrding to the situation of leishmaniasis in French Guiana(DEDET et al.. 19851we assumethat all cases except onewere due to L. 6. guyanensis. The isolates of six casesare maintained in culture and mass cultivation is in progress for further isoenzyme identification. The treatment consistedin a 400 mg (two tablets) daily oral doseof ketoconazoleduring 30 days. When the lesionsweresuperinfected(six cases),the patients were also treated with antibiotics. The treatment was well tolerated and compatible with normal professionaland life activities. Minor
improved in only one case. Three patients developed new lesions during the course of treatment. By the end of the treatment, no clinical cure was observed and eight patients had lesionsstill harbouring para-
sites (positive smears). One month after the end of the treatment, a single patient was clinically cured and in a second patient the first lesion was cured but a second lesion was still
parasitized.A third patient wascured by the second month
following
the end of the treatment.
A second protocol of oral ketoconazole, using double dose (800 mg daily during 30 days), is in progress. We thank Janssen Pharmaceutics for providing us with the ketoconazole and the following medical doctors for providing us with the patients: M. Burlat, F. Lallemand, J. Michaudel, I. Ogorzelski and L. Salinier. JEAN-PIERRE DEDET PIERRE JAMET PHILIPPE ESTERRE PAUL MARIE GHIPPONI CLAUDE GENIN GERARD LALANDE Institut Pasteur de Guyane, Fraqaise, 97306 Cayenne Cedex, French Guiana. References
Dedet, J. P., Pradinaud, R., Desjeux, I’., Jacquet-Viallet, P., Girardeau, I., Esterre P. & GGtz, W. (1985). Deux nremiers cas de leishmaniose cutanCe & Leishmania keiicana amazonensis en Guyane fran@e. Bulletin de la Socild
de l’athologie
exotique,
78, 64-70.
Weinrauch, L., Livshin, R., Even-Paz, Z. & El-On, J. (1983). Efficacy of ketoconazole in cutaneous leishmaniasis. Archives of Dermatological Research, 215, 353354. Weinrauch, L., Livshin, R. & El-On. J. (1984). Comparative study of the efficacy of ketoconazole and rifampicin in the treatment of cutaneous leishmaniasis. Proceedings of the’ Fourth European Multicolloquium of Parasitology, Z.&r, 69-70.
side effects were seen in nine patients (asthenia-six,
sleepiness-two,
pain-two)
without
nervousness-two, necessitating
epigastric
interruption
of the
Accepted for publication
13th August, 1985.