Mycoplasma Pneumoniae Infections Associated with Severe Mucositis Sherman J. Alter, MD*, Brenda
Infections caused
monly result in
by Mycoplasma pneumoniae compneumonia in children and adults. It is well
known, however, that infections with these agents may result in
variety of extrapulmonary diseases. We report temporal cluster of cases involving children with Mycoplasma pneumoniae respiratory infections who also a
a
presented with severe mucositis. Case Discussions Case 1 On October 13, 1989, a 13-year-old male was admitted The Children’s Medical Center with fever, painful mouth lesions and cough. Two weeks prior to admission he was treated with a course of oral penicillin for bronchitis. He did not improve within five days of therapy and was subsequently treated, in succession, with several days of oral cephalexin, amoxicillin-clavulinate and erythromycin-sulfasoxazole. Three days prior to admission, painful mouth sores, eye pain and dysuria developed and he refused to eat or drink. On admission, he presented with a temperature of 38.2°C, heart rate of 32. He was an ill-appearing child. He had markedly injected conjunctivae bilaterally with scant yellow discharge. The oropharynx had diffuse ulcerations to
*
The Children’s Medical Center, Department of Pediatrics, Wright University School of Medicine, Dayton, OH. Correspondence to: Department of Pediatrics, The Children’s Medical Center, 1 Children’s Plaza, Dayton, OH 45404-1815.
State
Stringer, MD*
and scattered hemorrhagic areas. Rakes were heard at the right lung base posteriorly. There was no hepatosplenomegaly or lymphadenopathy. The genitalia and extremities were unremarkable. He had no rash. His white blood cell was 13.6 x 103 with 73% polymorphonuclear cells and 6% bands. The erythrocyte sedimentation rate was 48 mm/hr. The chest radiograph was normal. An acute M. pneumoniae complement fixation Blood cultures were sterile. A urinalysis titre was >256. was normal. A swab of oropharyngeal ulcers for viral isolation was inoculated on to Rhesus monkey kidney, HEP-2 and MRC-5 human fibroblast cell cultures. No viruses were isolated. He responded quickly to intravenous hydration and local mouth and eye care. He was given two days of intravenous erythromycin and was discharged to complete a 14 day course of oral erythromycin. Acute and one month convalescent serum specimens were frozen and assayed in parallel for M. pneumoniae complement fixation titres. A four decrease in titres occurred.
Case 2 On October 14, 1989 a 10 year old male was admitted with dehydration, dysphagia, and cough. Six days prior to admission he was seen with a complaint of sore throat. A throat culture grew scant amounts of group A beta-hemolytic streptococci and the patient was treated with amoxicillin. Three days prior to admission he was unable to ingest anything orally because of persistent and worsening throat and mouth pain. He developed a non-
productive cough.
602
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
Physical examination revealed an uncomfortable-appearing boy. He was febrile with a temperature of 39.3 C., heart rate of 96, and respiratory rate of 32. He was unable to open his mouth because of a yellow-gray pseudomembrane essentially cementing his lips together. Eventual examination of the oropharynx revealed diffuse areas of hemorrhage with scattered ulcerations and marked generalized erythema. There was a left otitis media with bullae on the tympanic membrane. Both conjunctivae were injected. There were several small, nontender anterior cervical lymph nodes bilaterally. Bibasilar rales were ascultated. There was no hepatosplenomegaly or rash. The remainder of the physical examination was normal. The white blood cell count was 10.8X103 with 73% polymorphonuclear cells and 15% bands. The hemoglobin was 10.8 gm/dl with a hematocrit of 31.8%. A chest radiograph demonstrated diffuse interstitial infiltrates bilaterally. Blood cultures were sterile. A culture of oropharyngeal ulcers yielded no viruses. IgM and IgG antibody titres for Epstein-Barr virus were < 16. An acute mycoplasma complement fixation titre was >256. The child was treated with intravenous hydration, intravenous erythromycin and local eye and mouth care. On the second day of hospitalization he complained of dysuria. The urethral meatus was erythematous and had a yellow discharge. A urinalysis was normal and urine bacterial cultures were sterile. Urethral cultures were negative for chlamydia and gonococci. The patient became afebrile after six days of hospitalization. Within four days of hospitalization, symptoms of dysuria abated. Oral intake improved gradually as his mouth lesions resolved. He was discharged after 10 days of hospitalization to complete a two week course of oral erythromycin. A serum sample obtained four weeks after admission revealed a greater than four fold decrease in M. pneumoniae complement fixation titres.
Case 3 On October 25, 1989 a 12-year-old male was admitted with fever, cough, sore throat and emesis. He was seen by his physician five days prior to admission complaining of sore throat, painful mouth lesions, and a cough with intermittent post-tussive emesis. He was treated with oral and intramuscular penicillin for &dquo;bronchitis&dquo;. A throat culture grew normal oral flora. Symptoms worsened despite intramuscular injections of penicillin and vitamin B-12. He was unable to drink liquids for two days prior to admission. He complained of dysuria on the day of admission.
Physical examination revealed an irritable patient.
He febrile with a temperature of 39.0 C, heart rate of 145, and respiratory rate of 28. There was bilateral conjunctival edema and erythema with a scant amount of thin yellow discharge. The oropharynx was diffusely ulcerated with a white-gray pseudomembrane on the tongue and posterior pharynx. Rales were heard bilaterally at the lung base. There was no hepatosplenomegaly or lymphadenopathy. The urethral meatus was erythematous with a thin white discharge. There was no exanthem. The remainder of the physical examination was normal. The white blood cell count was 16.8X103 with 59% polymorphonuclear cells and 20% bands. Room air oxygen saturation by pulse oximetry was 93%; oxygen saturation on 30% inspired oxygen was 96%. Urethral, conjunctival and oral cultures did not yield bacterial pathogens or viruses. Blood cultures were sterile. Chest roentgenogram revealed a right upper lobe reticular lung density. Acute M. pneumoniae complement fixation titre was >256. The patient gradually improved with intravenous hydration, intravenous erythromycin and local care to the oropharynx, eyes and urethra. He was discharged after six hospital days to complete a 14 day course of oral erythromycin. On the day of discharge, the patient no longer complained of dysuria. A convalescent M. pneumoniae titre obtained four weeks later revealed a greater than fourfold decrease from the acute serum specimen. was
Discussion
Mycoplasma pneumoniae is primarily a pathogen of the respiratory tract, causing illness ranging from mild upper respiratory symptoms to fulminant pneumonia. Infection with this agent is estimated to be responsible for 5-20% of community acquired pneumonias.’ Symptoms consist of cough, fever and myalgia, and generally resolve within The disease is most common in children and young adults. Extrapulmonary manifestations are not rare, and include autoimmune hemolytic anemia, central and peripheral nervous system disease, disseminated intravascular coagulation, hepatitis, myo-and pericarditis, arthropathy, and Stevens-Johnson syndrome. While M. pneumoniae has been postulated to be a cause of bullous myringitis, it may be more likely that such inflammation of the tympanic membrane, as in our case #2, may represent a nonspecific reaction to infection.’ StevensJohnson syndrome has been reported to occur in 1.24.2% 1,3 of patients with M. pneumoniae infection. The complete syndrome consists of the typical erythema multiforme rash with target lesions and severe mucositis involving at least two surfaces (exudative con two to three weeks.
603
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
junctivitis, oral ulcers, vesicles, and exudate, and/or penile or vulvar ulcerations). It frequently is accompanied by fever, systemic toxicity and lymphadenitis. The illness may be acute or episodic, lasting one to six weeks. Some authors utilize the term Stevens-Johnson syndrome solely in patients with the typical exanthems.~ Others allow that some patients may not develop exanthems and indeed may only have mucosal surfaces affected. 6.7 The association of M. pneumoniae infection with Stevens-Johnson syndrome has been documented both by the presence of high titres of serum antibody to M. pneumoniae and by culture of the organism from the respiratory tract’ and cutaneous bullous fluid.’ M. pneumoniae infection-associated Stevens-Johnson syndrome usually occurs in children or young adults after a significant respiratory infection, although it has also been reported in an older adult’° and in cases where there were no significant respiratory symptoms. There is a large male to female predominance varying from 3:12 to 4:1.&dquo; Males tend to have more severe diseases, with more extensive mucosal involvement and bullous skin lesions. Recurrences are uncommon, but have been reported. 4,12 Patients who develop Stevens-Johnson syndrome in association with M. pneumoniae commonly tend to have received one or more courses of antibiotics before developments of the exanthem.2°m Our cases two and three received one antibiotic each, while case one was treated with four different antibiotics prior to hospital admission. Each, however, had serologic findings consistent with M. pneumoniae infection. The relationships, or lack thereof, among antibiotic utilization, M. pneumoniae infection, and Stevens-Johnson syndrome remain difficult to define. Our patients presented within a two week period. They were preadolescent males treated with one to several courses of antibiotics. No obvious geographic, contact, or other epidemiologic link was evident among the three. During this same time period no increase in the number of respiratory diseases or diagnosed mycoplasma disease were evident in the community. Each patient developed severe conjunctivitis, generalized ulcerative stomatitis and pharyngitis, urethritis and fever associated with M. pneumoniae respiratory infection. None of the three patients developed an exanthem. Previously reported cases of M. pneumoniae infection associated with StevensJohnson syndrome have included some type of rash, ranging from typical generalized lesions which evolve to bullae or crusts to only a few target lesions.&dquo;I In summary, our cases represent an unusual clustered presentation of children with inflammation of several mucous membranes associated with M. pnuemoniae res-
The diagnosis of mycoplasma infection should be entertained in patients presenting with similar clinical pictures. Such cases may represent one type of clinical presentation within the spectrum of StevensJohnson syndrome. Alternatively, M. pneumoniae may be directly involved in causing the mucosal pathology noted in our cases.
piratory infection.
References 1. Ali
NJ, Sillis M, Andrews BE,
et
al. The clinical spectrum and infection. Quart Med
diagnosis of mycoplasma pneumoniae 1986;58:241-51.
2. Roberts D. The etiology of bullous myringitis and the role of mycoplasma in disease. A review. Pediatr 1980;65:761-6. 3. McCormack JG. Mycoplasma pneumoniae and the erythema multiforme-Stevens-Johnson syndrome. J Infect 1981; 3:32-6. 4. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristic, diagnostic criteria, and causes.
Am Acad Derm 1983;8:763-75. 5. McKellar GM, Rease PC. Erythema multiforme and mycoplasma pnuemoniae infection. Int J Oral Maxillofacial Surg 1986;15: 342-8. 6. Kennett S. Erythema multiforme affecting the oral cavity. Oral
Surg 1968;25:366-73. 7. Bean SF, Quezada RK. Recurrent oral erythema multiforme. JAMA 1983;249:2810-12. 8. Edmond BJ, Huff JC, Weston WL. Erythema multiforme. Pediatr Clin Am 1983;30:631-40. 9. Stutman HR. Stevens-Johnson syndrome and mycoplasma pneumoniae: Evidence of cutaneous infection. J Pediatr
1987;111:845-7. 10. Kalb RE, Grossman ME, Neu HC. Stevens-Johnson syndrome due to mycoplasma pneumoniae in an adult. Am J Med 1985;79: 541-4. 11. Cherry JD, Hurwitz ES, Welliver RC. Mycoplasma pneumoniae infection and exanthems. J Pediatr 1975;87:369-73. 12. Welch KJ, Burke WA, Irons TG. Recurrent erythema multiforme due to mycoplasma pneumoniae. J Am Acad Derm 1987; 17 :38940.
604
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
Infections caused
monly result in
by Mycoplasma pneumoniae compneumonia in children and adults. It is well
known, however, that infections with these agents may result in
variety of extrapulmonary diseases. We report temporal cluster of cases involving children with Mycoplasma pneumoniae respiratory infections who also a
a
presented with severe mucositis. Case Discussions Case 1 On October 13, 1989, a 13-year-old male was admitted The Children’s Medical Center with fever, painful mouth lesions and cough. Two weeks prior to admission he was treated with a course of oral penicillin for bronchitis. He did not improve within five days of therapy and was subsequently treated, in succession, with several days of oral cephalexin, amoxicillin-clavulinate and erythromycin-sulfasoxazole. Three days prior to admission, painful mouth sores, eye pain and dysuria developed and he refused to eat or drink. On admission, he presented with a temperature of 38.2°C, heart rate of 32. He was an ill-appearing child. He had markedly injected conjunctivae bilaterally with scant yellow discharge. The oropharynx had diffuse ulcerations to
*
The Children’s Medical Center, Department of Pediatrics, Wright University School of Medicine, Dayton, OH. Correspondence to: Department of Pediatrics, The Children’s Medical Center, 1 Children’s Plaza, Dayton, OH 45404-1815.
State
Stringer, MD*
and scattered hemorrhagic areas. Rakes were heard at the right lung base posteriorly. There was no hepatosplenomegaly or lymphadenopathy. The genitalia and extremities were unremarkable. He had no rash. His white blood cell was 13.6 x 103 with 73% polymorphonuclear cells and 6% bands. The erythrocyte sedimentation rate was 48 mm/hr. The chest radiograph was normal. An acute M. pneumoniae complement fixation Blood cultures were sterile. A urinalysis titre was >256. was normal. A swab of oropharyngeal ulcers for viral isolation was inoculated on to Rhesus monkey kidney, HEP-2 and MRC-5 human fibroblast cell cultures. No viruses were isolated. He responded quickly to intravenous hydration and local mouth and eye care. He was given two days of intravenous erythromycin and was discharged to complete a 14 day course of oral erythromycin. Acute and one month convalescent serum specimens were frozen and assayed in parallel for M. pneumoniae complement fixation titres. A four decrease in titres occurred.
Case 2 On October 14, 1989 a 10 year old male was admitted with dehydration, dysphagia, and cough. Six days prior to admission he was seen with a complaint of sore throat. A throat culture grew scant amounts of group A beta-hemolytic streptococci and the patient was treated with amoxicillin. Three days prior to admission he was unable to ingest anything orally because of persistent and worsening throat and mouth pain. He developed a non-
productive cough.
602
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
Physical examination revealed an uncomfortable-appearing boy. He was febrile with a temperature of 39.3 C., heart rate of 96, and respiratory rate of 32. He was unable to open his mouth because of a yellow-gray pseudomembrane essentially cementing his lips together. Eventual examination of the oropharynx revealed diffuse areas of hemorrhage with scattered ulcerations and marked generalized erythema. There was a left otitis media with bullae on the tympanic membrane. Both conjunctivae were injected. There were several small, nontender anterior cervical lymph nodes bilaterally. Bibasilar rales were ascultated. There was no hepatosplenomegaly or rash. The remainder of the physical examination was normal. The white blood cell count was 10.8X103 with 73% polymorphonuclear cells and 15% bands. The hemoglobin was 10.8 gm/dl with a hematocrit of 31.8%. A chest radiograph demonstrated diffuse interstitial infiltrates bilaterally. Blood cultures were sterile. A culture of oropharyngeal ulcers yielded no viruses. IgM and IgG antibody titres for Epstein-Barr virus were < 16. An acute mycoplasma complement fixation titre was >256. The child was treated with intravenous hydration, intravenous erythromycin and local eye and mouth care. On the second day of hospitalization he complained of dysuria. The urethral meatus was erythematous and had a yellow discharge. A urinalysis was normal and urine bacterial cultures were sterile. Urethral cultures were negative for chlamydia and gonococci. The patient became afebrile after six days of hospitalization. Within four days of hospitalization, symptoms of dysuria abated. Oral intake improved gradually as his mouth lesions resolved. He was discharged after 10 days of hospitalization to complete a two week course of oral erythromycin. A serum sample obtained four weeks after admission revealed a greater than four fold decrease in M. pneumoniae complement fixation titres.
Case 3 On October 25, 1989 a 12-year-old male was admitted with fever, cough, sore throat and emesis. He was seen by his physician five days prior to admission complaining of sore throat, painful mouth lesions, and a cough with intermittent post-tussive emesis. He was treated with oral and intramuscular penicillin for &dquo;bronchitis&dquo;. A throat culture grew normal oral flora. Symptoms worsened despite intramuscular injections of penicillin and vitamin B-12. He was unable to drink liquids for two days prior to admission. He complained of dysuria on the day of admission.
Physical examination revealed an irritable patient.
He febrile with a temperature of 39.0 C, heart rate of 145, and respiratory rate of 28. There was bilateral conjunctival edema and erythema with a scant amount of thin yellow discharge. The oropharynx was diffusely ulcerated with a white-gray pseudomembrane on the tongue and posterior pharynx. Rales were heard bilaterally at the lung base. There was no hepatosplenomegaly or lymphadenopathy. The urethral meatus was erythematous with a thin white discharge. There was no exanthem. The remainder of the physical examination was normal. The white blood cell count was 16.8X103 with 59% polymorphonuclear cells and 20% bands. Room air oxygen saturation by pulse oximetry was 93%; oxygen saturation on 30% inspired oxygen was 96%. Urethral, conjunctival and oral cultures did not yield bacterial pathogens or viruses. Blood cultures were sterile. Chest roentgenogram revealed a right upper lobe reticular lung density. Acute M. pneumoniae complement fixation titre was >256. The patient gradually improved with intravenous hydration, intravenous erythromycin and local care to the oropharynx, eyes and urethra. He was discharged after six hospital days to complete a 14 day course of oral erythromycin. On the day of discharge, the patient no longer complained of dysuria. A convalescent M. pneumoniae titre obtained four weeks later revealed a greater than fourfold decrease from the acute serum specimen. was
Discussion
Mycoplasma pneumoniae is primarily a pathogen of the respiratory tract, causing illness ranging from mild upper respiratory symptoms to fulminant pneumonia. Infection with this agent is estimated to be responsible for 5-20% of community acquired pneumonias.’ Symptoms consist of cough, fever and myalgia, and generally resolve within The disease is most common in children and young adults. Extrapulmonary manifestations are not rare, and include autoimmune hemolytic anemia, central and peripheral nervous system disease, disseminated intravascular coagulation, hepatitis, myo-and pericarditis, arthropathy, and Stevens-Johnson syndrome. While M. pneumoniae has been postulated to be a cause of bullous myringitis, it may be more likely that such inflammation of the tympanic membrane, as in our case #2, may represent a nonspecific reaction to infection.’ StevensJohnson syndrome has been reported to occur in 1.24.2% 1,3 of patients with M. pneumoniae infection. The complete syndrome consists of the typical erythema multiforme rash with target lesions and severe mucositis involving at least two surfaces (exudative con two to three weeks.
603
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
junctivitis, oral ulcers, vesicles, and exudate, and/or penile or vulvar ulcerations). It frequently is accompanied by fever, systemic toxicity and lymphadenitis. The illness may be acute or episodic, lasting one to six weeks. Some authors utilize the term Stevens-Johnson syndrome solely in patients with the typical exanthems.~ Others allow that some patients may not develop exanthems and indeed may only have mucosal surfaces affected. 6.7 The association of M. pneumoniae infection with Stevens-Johnson syndrome has been documented both by the presence of high titres of serum antibody to M. pneumoniae and by culture of the organism from the respiratory tract’ and cutaneous bullous fluid.’ M. pneumoniae infection-associated Stevens-Johnson syndrome usually occurs in children or young adults after a significant respiratory infection, although it has also been reported in an older adult’° and in cases where there were no significant respiratory symptoms. There is a large male to female predominance varying from 3:12 to 4:1.&dquo; Males tend to have more severe diseases, with more extensive mucosal involvement and bullous skin lesions. Recurrences are uncommon, but have been reported. 4,12 Patients who develop Stevens-Johnson syndrome in association with M. pneumoniae commonly tend to have received one or more courses of antibiotics before developments of the exanthem.2°m Our cases two and three received one antibiotic each, while case one was treated with four different antibiotics prior to hospital admission. Each, however, had serologic findings consistent with M. pneumoniae infection. The relationships, or lack thereof, among antibiotic utilization, M. pneumoniae infection, and Stevens-Johnson syndrome remain difficult to define. Our patients presented within a two week period. They were preadolescent males treated with one to several courses of antibiotics. No obvious geographic, contact, or other epidemiologic link was evident among the three. During this same time period no increase in the number of respiratory diseases or diagnosed mycoplasma disease were evident in the community. Each patient developed severe conjunctivitis, generalized ulcerative stomatitis and pharyngitis, urethritis and fever associated with M. pneumoniae respiratory infection. None of the three patients developed an exanthem. Previously reported cases of M. pneumoniae infection associated with StevensJohnson syndrome have included some type of rash, ranging from typical generalized lesions which evolve to bullae or crusts to only a few target lesions.&dquo;I In summary, our cases represent an unusual clustered presentation of children with inflammation of several mucous membranes associated with M. pnuemoniae res-
The diagnosis of mycoplasma infection should be entertained in patients presenting with similar clinical pictures. Such cases may represent one type of clinical presentation within the spectrum of StevensJohnson syndrome. Alternatively, M. pneumoniae may be directly involved in causing the mucosal pathology noted in our cases.
piratory infection.
References 1. Ali
NJ, Sillis M, Andrews BE,
et
al. The clinical spectrum and infection. Quart Med
diagnosis of mycoplasma pneumoniae 1986;58:241-51.
2. Roberts D. The etiology of bullous myringitis and the role of mycoplasma in disease. A review. Pediatr 1980;65:761-6. 3. McCormack JG. Mycoplasma pneumoniae and the erythema multiforme-Stevens-Johnson syndrome. J Infect 1981; 3:32-6. 4. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristic, diagnostic criteria, and causes.
Am Acad Derm 1983;8:763-75. 5. McKellar GM, Rease PC. Erythema multiforme and mycoplasma pnuemoniae infection. Int J Oral Maxillofacial Surg 1986;15: 342-8. 6. Kennett S. Erythema multiforme affecting the oral cavity. Oral
Surg 1968;25:366-73. 7. Bean SF, Quezada RK. Recurrent oral erythema multiforme. JAMA 1983;249:2810-12. 8. Edmond BJ, Huff JC, Weston WL. Erythema multiforme. Pediatr Clin Am 1983;30:631-40. 9. Stutman HR. Stevens-Johnson syndrome and mycoplasma pneumoniae: Evidence of cutaneous infection. J Pediatr
1987;111:845-7. 10. Kalb RE, Grossman ME, Neu HC. Stevens-Johnson syndrome due to mycoplasma pneumoniae in an adult. Am J Med 1985;79: 541-4. 11. Cherry JD, Hurwitz ES, Welliver RC. Mycoplasma pneumoniae infection and exanthems. J Pediatr 1975;87:369-73. 12. Welch KJ, Burke WA, Irons TG. Recurrent erythema multiforme due to mycoplasma pneumoniae. J Am Acad Derm 1987; 17 :38940.
604
Downloaded from cpj.sagepub.com at NANYANG TECH UNIV LIBRARY on May 21, 2015
