Dengue: muscle biopsy findings in 15 patients

Malheiros, S.M.F.; Oliveira, A.S.B.; Schmidt, B.; Lima, J.G. Camargo; Gabbai, A.A.

doi:10.1590/S0004-282X1993000200001

Abstracts

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

dengue; muscle; myalgia

A síndrome clínica produzida pelo vírus da dengue, inclui febre, exantema, cefaléia e especialmente mialgia. Entretanto, as possiveis alterações morfológicas do músculo esquelético, eventualmente relacionadas com a mialgia, ainda não haviam sido estudadas em seres humanos com dengue. Nosso objetivo foi estudar o substrato, anatomopatológico da mialgia nesses pacientes. Foram avaliados 15 pacientes com diagnóstico de dengue, forma clássica, com idades variando de 14 a 47 anos (mediana de 23 anos), sendo 4 do sexo masculino e 11 do sexo feminino, através de exame clínico e neurológico, exames laboratoriais e biópsia muscular com histoquímica, durante a epidemia de dengue em Alagoas, em 1987. Todos os pacientes apresentavam história de cefaléia, febre e mialgia intensa, sem fraqueza muscular. Ao exame clínico observou-se exantema em 4 pacientes, febre em 3 e discreta hepatomegalia em 3. O exame neurológico foi normal em todos e a enzima CK sérica estava pouco elevada em 3 pacientes. A biópsia muscular revelou discreto infiltrado inflamatório mononuclear perivascular em 12 pacientes, acúmulo lipídico em 11, predominância de fibras do tipo I em 6, raros focos de necrose em 3, proliferação mitocondrial em 3, centralização nuclear em 3 e "type grouping" em 2. As alterações mais frequentemente observadas na biópsia muscular, infiltrado inflamatório perivascular e acúmulo lipídico, podem estar relacionadas com a mialgia.

dengue; músculo; mialgia

S.M.F. Malheiros^I; A.S.B. Oliveira^I; B. Schmidt^II; J.G. Camargo Lima^I; A.A. Gabbai^I

^IDepartment of Neurology, Escola Paulista de Medicina, São Paulo

^IIDepartment of Pathology, Escola Paulista de Medicina, São Paulo

SUMMARY

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

Key words: dengue, muscle, myalgia.

RESUMO

A síndrome clínica produzida pelo vírus da dengue, inclui febre, exantema, cefaléia e especialmente mialgia. Entretanto, as possiveis alterações morfológicas do músculo esquelético, eventualmente relacionadas com a mialgia, ainda não haviam sido estudadas em seres humanos com dengue. Nosso objetivo foi estudar o substrato, anatomopatológico da mialgia nesses pacientes. Foram avaliados 15 pacientes com diagnóstico de dengue, forma clássica, com idades variando de 14 a 47 anos (mediana de 23 anos), sendo 4 do sexo masculino e 11 do sexo feminino, através de exame clínico e neurológico, exames laboratoriais e biópsia muscular com histoquímica, durante a epidemia de dengue em Alagoas, em 1987. Todos os pacientes apresentavam história de cefaléia, febre e mialgia intensa, sem fraqueza muscular. Ao exame clínico observou-se exantema em 4 pacientes, febre em 3 e discreta hepatomegalia em 3. O exame neurológico foi normal em todos e a enzima CK sérica estava pouco elevada em 3 pacientes. A biópsia muscular revelou discreto infiltrado inflamatório mononuclear perivascular em 12 pacientes, acúmulo lipídico em 11, predominância de fibras do tipo I em 6, raros focos de necrose em 3, proliferação mitocondrial em 3, centralização nuclear em 3 e "type grouping" em 2. As alterações mais frequentemente observadas na biópsia muscular, infiltrado inflamatório perivascular e acúmulo lipídico, podem estar relacionadas com a mialgia.

Palavras-chave: dengue, músculo, mialgia.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Aknowledgements We are grateful to Dr. Fernando Lira Neto for referring the patients to us and for his assistance during our stay in Maceió, to Instituto Adolfo Lutz (São Paulo, SP, Brasil) for performing the IgM antibody detections by Mac ELISA and the virus isolation, and to Instituto Evandro Chagas (Belém, PA, Brasil) for performing the hemagglutination inhibition tests.

Aceite: 08-novembro-1992.

Dr. Acary S.B. Oliveira Department of Neurology, Escola Paulista de Medicina Rua Botucatu 720 04023-900 São Paulo SP Brasil.

1. Agrawal DK, Tandon P, Chaturvedi UC, Kumar A. Biochemical study of certain enzymes (and metabolites of the carbohydrate metabolism in skeletal muscle of the dengue virus-infected mice. J Gen Virol 1978, 40:399-408.
²
Aids to the examination of the peripheral nervous system. London: Bailliere Tindall, 1986.
3. Banker BQ, Engel AG. Basic reactions of muscle. In Emgel AG, Banker BQ (eds): Myology. New York: McGraw Hill, 1986, Vol 1, p 845-907.
4. Bhamarapravati N, Tuchinda P, Boonyapaknavik U. Pathology of Thailand haemorrhagic fever: a study of 100 autopsy cases. Ann Trop Med Parasitol 1967, 61:500-510.
5. Carrada-Bravo T. La epidemiología del dengue en America 1982-1984: quinta parte. Salud Publ Mex 1987, 29:15-25.
6. Case Records of the Massachusetts General Hospital (Case 40-1989). N Engl J Med 1989, 321:957-965.
7. Chimelli L, Hahn MD, Netto MB, Ramos RG, Dias M, Gray F. Dengue: neuropatho-logical findings in 5 fatal cases from Brazil. Clin Neuropathol 1990, 9:157-162.
8. Dietz VJ, Gubler DJ, Rigau-Ferez JG, Pinheiro F, Schatzmayr G, Bailey R, Gunn RA. Epidemic dengue 1 in Brazil, 1986: evaluation of a clinically biased dengue surveillance system. Am J Epidemiol 1990, 131:693-701.
9. Dubowitz V. Muscle biopsy: a practical approach. (Ed 2). London: Bailliere Tindall, 1985, p 3-40.
10. Engel AG, Banker BQ. Ultrastructural changes in diseased muscle. In Engel AG, Banker BQ (eds): Myology. New York: McGraw Hill, 1986, Vol 1, p 909-1043.
11. Farrel MK, Partin JC, Boue KE. Epidemic influenza myopathy in Cincinnati in 1977. J Fediatr 1980, 96:545-551.
12. Gamboa ET, Eastwood AB, ays AP, Maxwell J, Penn AS. Isolation of influenza virus from muscle in myoglobinuric polymyositis. Neurology 1979, 29:1323-1335.
13. Halstead SB. Dengue haemorrhagic fever: a public health problem and a field of research. Bull WO 1980, 58:1-21.
14. Hays AP, Gamboa ET. Acute viral myositis. In Engel AG, Banker BQ (eds): Myology. New York: 1986, Vol 2, p 1439-1466.
15. Johnson MA, Polgar J, Leightman D, Pippelton D. Data on the distribution of fiber types in thirty-six human muscles: an autopsy study. J Neurol Sei 1973, 18:111-129.
16. Layzer RB. Muscle pain, cramps and fatigue. In Engel AG, Banker BQ (eds): Myology. New York: 1986, Vol. 2, 1907-1921.
17. Lepine P, Desse G, Sautter V. Biopsies musculaires avec examen histologique et isolement du virus Coxsackie chex l'homme atteint de myalgie epidemique (maladie de Born-holm). Bull Acad Nation Med 1952, 136:66-69.
18. Mastaglia FL, Ojeda UJ. Inflammatory myopathies: part 1. Ann Neurol 1985, 17:215-227.
19. Murphy FA, Kingsbury DW. Flaviviruses. In Fields BN et al. (eds): Virology Ed 2. New York: Raven Press, 1990, Vol 1, p 763-814.
20. Nath P, Agrawal DK, Mehrotra RML. Ultrastructurtal changes in skeletal muscles in dengue virus-infected mice. J Pathol 1982, 136:301-305.
21. Organizacion Mundial de la Salud. Dengue hemorragico: diagnostico tratamiento y lucha. OMS, Giniebra, 1987.
22. Pinheiro PF. Dengue in the Americas. Epidemiol Bull 1989, 10:1-8.
23. Roy EP, Gutmann L. Myalgia. In Riggs JE (eds): Neurologic Clinics: Muscle Disease. Philadelphia: W.B. Saunders, 1988, Vol 6, number 3, p 621-636.
24. Sahaphong S, Riengrojpitak S, Bhamarapravati N, Chirachariyavej T. Electron microscopic study of the vascular endothelial cell in dengue hemorrhagic fever. Southeast Asian J Trop Med Pub Hlth 1980, 11:194-204.

Dengue: muscle biopsy findings in 15 patients

Dengue: achados de biópsia muscular em 15 pacientes

Publication Dates

Publication in this collection
19 Jan 2011
Date of issue
June 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Agrawal DK, Tandon P, Chaturvedi UC, Kumar A. Biochemical study of certain enzymes (and metabolites of the carbohydrate metabolism in skeletal muscle of the dengue virus-infected mice. J Gen Virol 1978, 40:399-408.

[2] ²
Aids to the examination of the peripheral nervous system. London: Bailliere Tindall, 1986.

[3] 3. Banker BQ, Engel AG. Basic reactions of muscle. In Emgel AG, Banker BQ (eds): Myology. New York: McGraw Hill, 1986, Vol 1, p 845-907.

[4] 4. Bhamarapravati N, Tuchinda P, Boonyapaknavik U. Pathology of Thailand haemorrhagic fever: a study of 100 autopsy cases. Ann Trop Med Parasitol 1967, 61:500-510.

[5] 5. Carrada-Bravo T. La epidemiología del dengue en America 1982-1984: quinta parte. Salud Publ Mex 1987, 29:15-25.

[6] 6. Case Records of the Massachusetts General Hospital (Case 40-1989). N Engl J Med 1989, 321:957-965.

[7] 7. Chimelli L, Hahn MD, Netto MB, Ramos RG, Dias M, Gray F. Dengue: neuropatho-logical findings in 5 fatal cases from Brazil. Clin Neuropathol 1990, 9:157-162.

[8] 8. Dietz VJ, Gubler DJ, Rigau-Ferez JG, Pinheiro F, Schatzmayr G, Bailey R, Gunn RA. Epidemic dengue 1 in Brazil, 1986: evaluation of a clinically biased dengue surveillance system. Am J Epidemiol 1990, 131:693-701.

[9] 9. Dubowitz V. Muscle biopsy: a practical approach. (Ed 2). London: Bailliere Tindall, 1985, p 3-40.

[10] 10. Engel AG, Banker BQ. Ultrastructural changes in diseased muscle. In Engel AG, Banker BQ (eds): Myology. New York: McGraw Hill, 1986, Vol 1, p 909-1043.

[11] 11. Farrel MK, Partin JC, Boue KE. Epidemic influenza myopathy in Cincinnati in 1977. J Fediatr 1980, 96:545-551.

[12] 12. Gamboa ET, Eastwood AB, ays AP, Maxwell J, Penn AS. Isolation of influenza virus from muscle in myoglobinuric polymyositis. Neurology 1979, 29:1323-1335.

[13] 13. Halstead SB. Dengue haemorrhagic fever: a public health problem and a field of research. Bull WO 1980, 58:1-21.

[14] 14. Hays AP, Gamboa ET. Acute viral myositis. In Engel AG, Banker BQ (eds): Myology. New York: 1986, Vol 2, p 1439-1466.

[15] 15. Johnson MA, Polgar J, Leightman D, Pippelton D. Data on the distribution of fiber types in thirty-six human muscles: an autopsy study. J Neurol Sei 1973, 18:111-129.

[16] 16. Layzer RB. Muscle pain, cramps and fatigue. In Engel AG, Banker BQ (eds): Myology. New York: 1986, Vol. 2, 1907-1921.

[17] 17. Lepine P, Desse G, Sautter V. Biopsies musculaires avec examen histologique et isolement du virus Coxsackie chex l'homme atteint de myalgie epidemique (maladie de Born-holm). Bull Acad Nation Med 1952, 136:66-69.

[18] 18. Mastaglia FL, Ojeda UJ. Inflammatory myopathies: part 1. Ann Neurol 1985, 17:215-227.

[19] 19. Murphy FA, Kingsbury DW. Flaviviruses. In Fields BN et al. (eds): Virology Ed 2. New York: Raven Press, 1990, Vol 1, p 763-814.

[20] 20. Nath P, Agrawal DK, Mehrotra RML. Ultrastructurtal changes in skeletal muscles in dengue virus-infected mice. J Pathol 1982, 136:301-305.

[21] 21. Organizacion Mundial de la Salud. Dengue hemorragico: diagnostico tratamiento y lucha. OMS, Giniebra, 1987.

[22] 22. Pinheiro PF. Dengue in the Americas. Epidemiol Bull 1989, 10:1-8.

[23] 23. Roy EP, Gutmann L. Myalgia. In Riggs JE (eds): Neurologic Clinics: Muscle Disease. Philadelphia: W.B. Saunders, 1988, Vol 6, number 3, p 621-636.

[24] 24. Sahaphong S, Riengrojpitak S, Bhamarapravati N, Chirachariyavej T. Electron microscopic study of the vascular endothelial cell in dengue hemorrhagic fever. Southeast Asian J Trop Med Pub Hlth 1980, 11:194-204.