Clostridial Myonecrosis in an Adolescent Male

Melissa Langhan, MD, and Linda Arnold, MD

ABSTRACT. Extremity pain is a common complaint in and he was admitted to the hospital with a presumptive diagnosis adolescents. Pain out of proportion to examination find- of viral myositis for pain control, continued hydration, and mon- ings should raise suspicion of deep tissue infection. Clos- itoring of renal function. Within 2 hours of admission, he devel- tridial myonecrosis is a rapidly progressive disease con- oped a violaceous rash over his legs and became hypotensive. On examination, he was noted to have subcutaneous emphysema in sisting of muscle and systemic toxicity. It is both lower extremities. His legs were noted to be markedly en- usually seen in elderly and immunocompromised pa- larged, and distally they were cool and pale. The symptoms soon tients. Here we report a case of clostridial myonecrosis in spread to involve his right arm. Surgery was consulted and an an adolescent male. Pediatrics 2005;116:e735–e737. URL: emergent computed tomography scan was obtained, which www.pediatrics.org/cgi/doi/10.1542/peds.2004-2876; infec- showed gas extending from his calves to his psoas muscles bilat- tion, pain. erally and also in his right arm (Fig 1). Based on these findings, a diagnosis of was made. He received , , cefotaxime, and van- lostridial myonecrosis is a rare disease in the comycin. The patient was taken to the operating room for surgical United States, with an estimated incidence of debridement. He was then transferred to an outside institution for 900 to 1000 cases per year.1 However, its vir- hyperbaric therapy. On arrival after transport, he was C noted to have massive necrosis of his extremities and underwent ulent course and high mortality rate necessitate a bilateral disarticulations at the hips and removal of his right bicep high degree of suspicion among treating physicians. muscle. Blood and wound cultures grew septicum.He Here we present a case in an otherwise healthy teen- was given a final diagnosis of clostridial myonecrosis. ager and a review of the recent literature. After , he received antibiotic and hyperbaric oxygen therapy. His clinical course also necessitated intubation and vaso- CASE REPORT pressor treatment. Limited diagnostic testing for both immunode- ficiency and malignancies, including HIV testing, abdominal com- A previously healthy 17-year-old male presented to the emer- puted tomography scan, and immunoglobulin and complement gency department with a 2-day history of bilateral leg pain. The levels were negative at the outside institution. One month after his day before admission he was seen by his pediatrician and found to presentation, he was stable and transferred to a rehabilitation have , facial swelling, and oral ulcers. He was diagnosed with facility. He has had no additional infections, signs of immunode- a presumptive viral illness and treated with supportive measures. ficiency, or medical problems. He returned the next day with increasingly severe leg pain, and additional evaluation was undertaken. His past medical history consisted of a diagnosis of Epstein- DISCUSSION Barr virus 1 month before presentation from which he still com- plained of fatigue. He had done some light weight-lifting several Clostridial myonecrosis, also known as nontrau- days before the onset of pain but had no recent participation in matic or spontaneous , is an extremely organized sports activities. There was no history of trauma, and he rare occurrence in pediatric patients. The infection is denied drug or steroid use. characterized by muscle necrosis and systemic toxic- His initial vital signs were notable for a temperature of 39.1°C, respiratory rate of 32 breaths per minute, heart rate of 132 beats ity caused by several clostridial , the most per minute, and a blood pressure of 141/62 mm Hg. He was pale, notable of which is ␣-toxin (phospholipase C).2,3 diaphoretic, and unable to stand secondary to his pain. Mild C septicum, an anaerobic Gram-positive rod, is the orbital was present as well as gingival swelling and a single causative organism in the majority of cases, followed oral ulceration. There was severe tenderness involving both of his 4,5 thighs and his right calf muscles. by . Unlike typical cases of Urinalysis revealed hematuria and proteinuria and the absence gas gangrene, which follow trauma and are caused of red blood cells. Blood counts showed a count by C perfringens, the majority of cases of spontaneous of 2700/␮L (57% bands, 5% segmented neutrophils, 13% lympho- gas gangrene have no obvious external portal of cytes, 19% monocytes), and his creatine phosphokinase was ele- entry. The presumed source is mucosal defects of the vated at 3594 IU/L. His electrolytes and coagulation profile were 6 within normal limits. The erythrocyte sedimentation rate was 42 intestinal tract. C septicum is substantially more ae- mm/hour. rotolerant than C perfringens, and the inoculum re- Despite intravenous hydration and multiple doses of morphine quired for infection is 300 times smaller, which may and ketorolac, there was no improvement in the patient’s pain, explain the absence of a portal of entry.1 In the adult population, gas gangrene is often as- sociated with trauma, underlying immunodeficiency From the Department of Pediatric Emergency Medicine, Yale-New Haven states, venous insufficiency, or malignancy.7 Simi- Children’s Hospital, New Haven, Connecticut. Accepted for publication May 19, 2005. larly, in children, it has been associated with malig- doi:10.1542/peds.2004-2876 nancies, leukemia, neutropenia, and immunosup- No conflict of interest declared. pression.8,9 Spontaneous gas gangrene has a Address correspondence to Melissa Langhan, MD, Department of Pediatric particular association with colon cancer.3,4,10 In 1 Emergency Medicine, Yale-New Haven Children’s Hospital, 20 York St, WP 143, New Haven, CT 06851. E-mail: [email protected] review of spontaneous C septicum infections, 34% of PEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Acad- the patients were found to have colorectal cancer, emy of Pediatrics. and 40% were found to have a hematologic malig-

www.pediatrics.org/cgi/doi/10.1542/peds.2004-2876Downloaded from www.aappublications.org/newsPEDIATRICS by guest on September Vol. 11625, 2021 No. 5 November 2005 e735 Fig 1. Scout film demonstrating the presence of gas diffusely throughout the bilateral legs and right pelvis.

nancy.11 Those survivors of C septicum gas gangrene changes, pain, and systemic toxicity associated with who are found to be immunocompetent will produce this disease process.14 Aggressive surgical debride- antibodies to ␣-toxin.6 ment is the cornerstone of treatment for all of these The classic presentation of gas gangrene is that of soft tissue infections. severe pain and underlying crepitus. However, these The diagnosis of gas gangrene is based on clinical are frequently late symptoms; early findings are of- findings, demonstration of myonecrosis at surgery, ten nonspecific. Other symptoms include a sudden and supporting microbiological data. Bacteremia is onset of fever, abdominal pain, vomiting, diarrhea, documented in only 10% to 15% of patients with and rapid progression to shock. Up to 25% of pa- clostridial myonecrosis.6 Ultimately, gas gangrene is tients have myonecrosis at metastatic sites.11 a surgical diagnosis made when involved muscle is The sudden onset of severe pain is often the first visualized. The extent of myonecrosis is often greater symptom experienced by the patient. Typically, the than the skin changes indicate. pain is out of proportion to physical examination Treatment includes early operative debridement findings and is minimally relieved by medications. and antibiotic therapy. Because of the polymicrobial Initial physical examination of the site may be nor- nature of some necrotizing soft tissue infections, em- mal; within minutes to hours, localized tense edema, piric antibiotic coverage is implemented. Antibiotic pallor, and tenderness are seen.5–7 combinations used to treat gas gangrene usually in- Systemic findings include diaphoresis, tachycardia clude penicillin and clindamycin. Although high- disproportionate to temperature, and extreme anxi- dose penicillin was once the drug of choice for clos- ety on the part of the patient, who often remains tridial infections, it has been found to be less effective exceedingly alert until the very terminal stages. Late in severe disease. Clindamycin is beneficial because complications include intravascular , he- it has the ability to reduce the production of exotox- moglobinuria, , renal failure, and meta- ins produced by Clostridium species.1,7,13 bolic acidosis. The disease progresses rapidly over In some instances, hyperbaric oxygen therapy is the course of hours and is frequently fatal.3,5,7 also useful. The rationale for the use of hyperbaric The severity of the pain and presence of systemic oxygen includes the observations that raising local toxicity help to differentiate Clostridial myonecrosis tissue oxygen concentrations arrests clostridial repli- from other soft tissue infections including necrotiz- cation and ␣-toxin production and that hyperbaric ing fasciitis and crepitant cellulitis. Necrotizing fas- oxygen treatment of experimental animals reduces ciitis is frequently caused by group A ␤-hemolytic mortality.15 The use of hyperbaric oxygen therapy Streptococcus, but polymicrobial infections are also remains controversial. Clinical experience with hy- common. It is characterized by a rapid progression perbaric oxygen therapy suggest that, when used in and significant systemic toxicity. Skin findings are conjunction with surgery and antibiotics, it may re- often present early in the course of illness, and pain duce morbidity and mortality in cases of clostridial is present but to a lesser degree.12,13 Similar to myo- infection.16 Hyperbaric oxygen therapy, however, is necrosis, crepitant cellulitis can be caused by Clos- less useful in cases of C septicum than C perfringens tridium species; however, there are minimal skin because of the aerotolerant nature of this species.

e736 CLOSTRIDIAL MYONECROSISDownloaded from www.aappublications.org/news by guest on September 25, 2021 The progression of C septicum spontaneous gas 6. Lorber B. Gas gangrene and other Clostridium-associated diseases. In: gangrene may be even more fulminant than that of Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone, Inc; 2000: traumatic C perfringens gas gangrene. Despite opti- 2552–2556 mal management, the mortality rate is 67% to 100%, 7. Headley AJ. Necrotizing soft tissue infections: a primary care review. with most dying within 24 hours after onset.5 Am Fam Physician. 2003;68:323–328 This case of gas gangrene in a healthy adolescent 8. Keogh G, Unsworth I, Vowels M, Kern IB. Spontaneous Clostridium septicum myonecrosis in congenital neutropenia. AustNZJSurg. 1994; demonstrates that soft tissue infection can occur in 64:574–575 the absence of precipitating events and risk factors. 9. Temple AM, Thomas NJ. Gas gangrene secondary to Clostridium per- In summary, nontraumatic gas gangrene is a rare but fringens in pediatric oncology patients. Pediatr Emerg Care. 2004;20: life-threatening disease for which physicians must 457–459 10. Rai RK, Londhe S, Sinha S, Campbell AC, Aburiziq IS. Spontaneous retain a high index of suspicion. Early and aggressive bifocal Clostridium septicum gas gangrene. J Bone Joint Surg Br. 2001;83: treatment is essential to reduce the mortality associ- 115–116 ated with this infection. 11. Kornbluth AA, Danzig JB, Bernstein LH. Clostridium septicum infection and associated malignancy. Report of 2 cases and review of the litera- ture. Medicine (Baltimore). 1989;68:30–37 REFERENCES 12. Fustes-Morales A, Gutierrez-Castrellon P, Duran-Mckinster C, Orozco- Covarrubias L, Tamayo-Sanchez L, Ruiz-Maldonado R. Necrotizing 1. Valentine EG. Nontraumatic gas gangrene. Ann Emerg Med. 1997;30: fasciitis: report of 39 pediatric cases. Arch Dermatol. 2002;138:893–899 109–111 13. Brook I. Microbiology and management of infectious gangrene in chil- 2. Hatheway CL. Toxigenic . Clin Microbiol Rev. 1990;3:66–98 dren. J Pediatr Orthop. 2004;24:587–592 3. Burke MP, Opeskin K. Nontraumatic clostridial myonecrosis. Am J 14. Bryant P, Carapetis J, Matussek J, Curtis N. Recurrent crepitant cellulitis Forensic Med Pathol. 1999;20:158–162 caused by Clostridium perfringens. Pediatr Infect Dis J. 2002;21:1173–1174 4. Zelic M, Vukas D, Vukas D Jr, et al. Fulminant endogene gas gangrene 15. Hill GB, Osterhout S. Experimental effects of hyperbaric oxygen on in a previously healthy male. Scand J Infect Dis. 2004;36:388–389 selected clostridial species. I. In-vitro studies. J Infect Dis. 1972;125:17–25 5. Stevens DL, Musher DM, Watson DA, et al. Spontaneous, nontraumatic 16. Stephens MB. Gas gangrene: potential for hyperbaric oxygen therapy. gangrene due to Clostridium septicum. Rev Infect Dis. 1990;12:286–296 Postgrad Med. 1996;99:217–220, 224

Downloaded from www.aappublications.org/newswww.pediatrics.org/cgi/doi/10.1542/peds.2004-2876 by guest on September 25, 2021 e737 Clostridial Myonecrosis in an Adolescent Male Melissa Langhan and Linda Arnold Pediatrics 2005;116;e735 DOI: 10.1542/peds.2004-2876 originally published online September 30, 2005;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/116/5/e735 References This article cites 14 articles, 1 of which you can access for free at: http://pediatrics.aappublications.org/content/116/5/e735#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Infectious Disease http://www.aappublications.org/cgi/collection/infectious_diseases_su b Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 25, 2021 Clostridial Myonecrosis in an Adolescent Male Melissa Langhan and Linda Arnold Pediatrics 2005;116;e735 DOI: 10.1542/peds.2004-2876 originally published online September 30, 2005;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/116/5/e735

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2005 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on September 25, 2021