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Infectious myositis
Best Practice & Research Clinical Rheumatology Vol. 20, No. 6, pp. 1083e1097, 2006 doi:10.1016/j.berh.2006.08.005 available online at http://www.sciencedirect.com
4 Infectious myositis Nancy F. Crum-Cianflone*
MD, MPH, FACP
Staff, Infectious Disease Physician Infectious Disease Division, Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, CA 92134-1005, USA
Infectious myositis, an infection of the skeletal muscle(s), is uncommon. This clinical entity may be caused by viral, bacterial, fungal, and parasitic pathogens. Viral etiologies typically cause diffuse myalgias and/or myositis, whereas bacteria and fungi usually lead to a local myositis which may be associated with sites compromised by trauma or surgery and are more common among immunocompromised patients. Localized collections within the muscles are referred to as pyomyositis. Other pyogenic causes of myositis include gas gangrene, group A streptococcal myonecrosis, and other types of non-clostridial myonecrosis. Early recognition and treatment of these conditions are necessary as they may rapidly become life-threatening. Key words: myositis; pyomyositis; psoas abscess; group A streptococcus; Clostridium spp; trichinosis.
Myositis refers to inflammation of the muscles and may be due to infectious and noninfectious etiologies. This paper focuses on the infectious causes of myositis. Noninfectious etiologies include a broad range of clinical conditions, including idiopathic inflammatory myopathies (e.g. polymyositis) and myopathies associated with autoimmune disorders, medications, genetic disorders, endocrine diseases, and electrolyte disturbances (Table 1).1 Some non-infectious myopathies may be triggered by environmental agents, including microorganisms.2 For example, polymyositis may be triggered in genetically predisposed individuals by viruses such as coxsackievirus B1, human immunodeficiency virus (HIV), human T-lymphotrophic virus 1 (HTLV-1), hepatitis B, influenza, adenovirus, and echovirus. INFECTIOUS MYOSITIS The infectious causes of myositis, summarized in Table 2, include viral, bacterial, fungal, and parasitic pathogens.1,3e17 Some infections cause focal myositis, while others lead * Tel.: þ1 619 532 8134/40; Fax: þ1 619 532 8137. E-mail address: [email protected] 1521-6942/$ - see front matter ª 2006 Published by Elsevier Ltd.
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Table 1. Non-infectious etiologies of myositis. Idiopathic inflammatory myopathies Polymyositis Dermatomyositis Myositis associated with collagen vascular diseases Polyarteritis nodosum Wegener’s granulomatosis Systemic lupus erythematosus Sjogren’s syndrome Rheumatoid arthritis Scleroderma Polymyalgia rheumatica Mixed connective tissue disease Adult Still’s disease Vasculitis e leukocytoclastic, hypersensitivity Myositis associated with malignancies Inclusion body myositis Other forms of inflammatory myopathies Myositis associated with eosinophilia Myositis ossificans Giant-cell myositis Myopathies caused by medications and toxins Metabolic myopathies Disorders in glycogen metabolism Endocrine disorders Electrolyte abnormalities Nutritional Disease which may cause myopathic symptoms Neuropathic disorders Muscular dystrophies Others including diseases of the neuromuscular junction Medication-related adverse events
to diffuse involvement of the musculature (Table 3). Bacteria and fungi usually present as a focal myositis, whereas viral and parasitic pathogens are more likely to present as a diffuse myositis. Further, bacterial myositis may occur in association with areas of the body that have been injured or compromised by trauma, surgery, the presence of a foreign body, or ischemia. In addition, hosts that are immunocompromised have a higher risk of many types of myositis, including bacterial and fungal. Bacteria and other microorganisms may cause focal infections in the musculature such as with pyomyositis or psoas abscesses. Pyogenic myositis is classified as clostridial myonecrosis (gas gangrene), group A streptococcus necrotizing myositis, or a non-clostridial myositis such as anaerobic streptococcal myonecrosis.18 Certain infectious diseases can be associated with myalgias, with or without myositis, including e.g. influenza, dengue, Rocky Mountain spotted fever (Rickettsia rickettsii), infective endocarditis, Lyme disease (Borrelia burgdorferi), toxoplasmosis, HIV infection, HTLV-1, and other virus diseases (see Table 2). Influenza virus, especially B, may manifest as myositis, which typically affects the bilateral lower calves; cases of rhabdomyolysis have been described.12,19 Myalgias accompany endocarditis in
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Table 2. Infectious causes of myositis and/or myalgias. Viral: Adenovirus Coxsackieviruses, especially B Cytomegalovirus (CMV) Echovirus EpsteineBarr virus (EBV) Hepatitis B virus Human immunodeficiency virus (HIV) Human T-cell lymphotrophic virus type 1 (HTLV-1) Influenza virus Mumps virus Parvovirus Rubella virus Varicellaezoster virus (VZV) West Nile Virus (WNV) Bacterial Staphylococcus Streptococcus Gram-negative organisms: Enterobacteria (including Yersinia), Pseudomonas, Aeromonas, others Anaerobes: Clostridium, Bacteroides, Fusobacterium, Peptostreptococcus, others ‘Atypical bacteria’ Bartonella Borrelia burgdorferi (Lyme disease) Francisella tularensis Leptospira Mycobacteria tuberculosis and other species Mycoplasma pneumoniae Rickettsia (including Rocky Mountain spotted fever) Fungal Aspergillus Candida Cryptococcus Fusarium Pneumocystis Parasitic Echinococcus Microsporidia e Trachipleistophora, Pleistophora Schistosoma Spirometra mansonoides (sparganosis) Toxocara Toxoplasma Trichinella Trypanosoma cruzi
15% of cases and may be diffuse or focal.15 Lyme disease is associated with proximal muscle involvement; rarely orbital myositis may occur.16 Toxoplasmosis-associated myositis typically appears among immunocompromised patients, especially those with a low CD4 cell count, and resembles autoimmune polymyositis.13,20 The West
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Table 3. Classification of infectious myositis. Non-pyogenic, generalized: Myalgias Viruses: influenza, dengue, HIV infection, HTLV-1, hepatitis B, EpsteineBarr virus, cytomegalovirus Bacteria: Rocky Mountain spotted fever (Rickettsia rickettsii), infective endocarditis, Lyme disease (Borrelia burgdorferi) Parasitic: toxoplasmosis Pleurodynia Coxsackievirus B Myalgias with Trichinosis (Trichinella spiralis) eosinophilia Cysticercosis (Taenia solium) Other parasitic diseases Pyogenic, typically localized infection: Pyomyositis Usually Staphylococcus aureus; may involve streptococci (group A, B, C, G or S. pneumoniae), Gram-negative organisms, anaerobes, mycobacteria, fungi, or parasites. Psoas abscess Gram-negative bacilli, anaerobes, S. aureus, M. tuberculosis Gas gangrene Clostridium spp, usually C. perfringens, less frequently C. septicum and C. novyi Non-clostridial Group A streptococcal necrotizing myositis myositis Anaerobic streptococcal myonecrosis Other forms of bacterial myonecrosis
Nile Virus may also present with myalgias during the acute presentation of West Nile Fever; less than 1% of patients develop neurologic symptoms which may include acute flaccid paralysis due to involvement of the anterior horn of the spinal cord.17,21 Finally, coxsackievirus B may cause myalgias in the musculature of the rib cage referred to as the pleurodynia syndrome or Bornholm disease. Infections manifesting as myalgias occurring with eosinophilia are described below; they are parasitic in nature. PYOMYOSITIS Pyomyositis is an intramuscular infection which involves one or more of the skeletal muscle groups, and which is not a result of infection of adjacent skin, soft tissue, or bone (Table 3). It was originally described in the tropics, and originally named pyomyositis tropicans.22 In these areas, the pyomyositis accounts for 1e4% of hospitalizations and is often associated with trauma, nutritional deficiencies, and/or concomitant parasitic infections (e.g. migration of Toxocara or the guinea worm, Dracunculus).23,24 In the past few decades, cases have been increasingly described in the developed world, especially among immunocompromised people such as those with HIV infection, malignancies, rheumatologic conditions, or diabetes mellitus.25 A recent review described 84 cases among HIV-infected people.26 Intravenous drug users are also at heightened risk.27 The pathogenesis of pyomyositis involves the occurrence of transient bacteremia in the setting of muscular injury; the latter is necessary since the musculature is relatively resistant to infection, and although bacteremia is quite common, pyomyositis is not.28,29 Intensive exercise or local trauma have been suggested, but many patients do not have a consistent history.26 In addition to trauma, other factors may cause muscular injury, including concurrent medical conditions (e.g. HIV, diabetes mellitus) and medications (e.g. zidovudine, steroids). Patients with HIV have several risk factors
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for their increased susceptibility to developing pyomyositis, including HIV myopathy, drug-induced mitochondrial dysfunction, concurrent bacterial infections, high rates of S. aureus colonization, and impaired neutrophil function.30,31 Three stages of pyomyositis have been described. (1) The invasive stage involves infection of the muscle, which causes the muscle to become edematous and painful; aspiration is unrevealing at this stage since there is no focal collection. (2) The suppurative phase is characterized by formation of an abscess and usually occurs 1e3 weeks later, with aspiration revealing pus; most cases are diagnosed in this stage. (3) The last stage involves the systemic spread of the infection, leading to septicemia, multifocal abscesses, and shock.24 Presenting signs and symptoms during the first stage include localized pain, swelling, and fever. There is often no erythema or warmth of the overlying skin since the infection is deep within the muscle. As the abscess develops, increasing pain, swelling and a ‘woody’ texture to the overlying area (Table 4) may exist. Pyomyositis is frequently misdiagnosed in these early stages as a muscle strain, thrombosis, hematoma, septic arthritis, or osteomyelitis. Pyomyositis that involves the iliacus or the obturator internus may mimic septic arthritis of the hip; pyriformic pyomositis may simulate a spinal epidural abscess, and iliopsoas myositis may be confused with appendicitis.32e34 Among patients with HIV or other immunocompromising conditions, the presenting symptoms may be particularly subtle due to a poor host immune response to the infection. Typically, a single muscle group is involved; however, multifocal involvement is noted in approximately 20% of cases.26 Occasionally, cases present as a more diffuse process confused with idiopathic inflammatory myopathy or polymyositis.35 The most common locations include the large skeletal muscles of the lower extremities (especially the quadriceps femoris and gluteus group) and the trunk muscles. Regional adenitis is not found on examination. The diagnosis is established by radiological imaging of the area of infection by ultrasound, CT scan, or MRI. CT scanning is the most commonly employed since it provides good definition of the areas of involvement and is relatively quick. MRI provides the most precise imaging. Laboratory tests are non-specific; leukocytosis is typically present, but may be absent among neutropenic patients or those with endstage AIDS. The erythrocyte sedimentation rate is usually elevated. Eosinophilia may occur in tropical cases and usually reflects an underlying parasitic infection. Levels of creatine phosphokinase and aldolase are typically normal, despite muscular involvement by the infection. Blood cultures may be positive in 5e30% of cases, with higher rates of positivity in the developed world. The specific etiologic agent for pyomyositis is typically discovered at the time of drainage e most commonly via CT-guided aspiration or pigtail placement, or an open procedure. The most frequent organism is Staphylococcus aureus, accounting for up to 95% of tropical cases and approximately 70% of cases in the developed world. Recently, cases due to MRSA have been described.27,36 Several other microbes have also been described, including streptococci, gram-negative bacilli (including enteric organisms, Bartonella), anaerobes (Fusobacterium, Clostridium), mycobacteria (M. tuberculosis and M. avium complex), microsporidia (especially among AIDS patients), and fungi (Cryptococcus, Aspergillus, Pneumocystis carinii ( jiroveci), Candida, Fusarium).11,26,37 Anaerobes may be found when careful culture procedures are followed. Cases involving fungi or microsporidia usually occur among immunocompromised patients.10 Treatment usually consists of both antibiotics and surgical drainage; if the disease is recognized in stage 1, antibiotics alone are curative. Antibiotics should provide coverage against S. aureus, such as with a b-lactamase-resistant penicillin; among patients at risk for MRSA, vancomycin should be considered. Broad-spectrum agents with good gramnegative coverage should be contemplated, especially among immunocompromised
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Table 4. Clinical presentations and management of infectious myositis of various etiologies. Pyomyositis
Gas gangrene
Group A Anaerobic Streptococcal streptococcal Necrotizing Myositis myonecrosis
Predisposing Residence in a tropical condition(s) area; trauma; in the developed world: immunocompromising conditions (HIV, diabetes, cancer) Fever Moderate Onset Gradual
Local trauma or surgery; for Clostridium septicum, evaluate for underlying gastrointestinal disorder Moderate to high Acute with a 2e3-day incubation period
Often no underlying Local trauma medical conditions among the patients; may be related to minor trauma
Systemic toxicity
Significant
Minimal; sepsis may develop in the last stage of infection Pain Localized, moderate Swelling Minimal to moderate Crepitus/gas Absent in tissues Odor None
Early, severe Significant Present
Moderate to high May have a prodromal phase, followed by an acute presentation with increasing muscular symptoms May be associated with toxic shock-like syndrome Severe Significant Absent
Foul-smelling
None Uninvolved overlying skin to a violaceous appearance with bullae especially with concurrent necrotizing fasciitis Group A streptococcus
Appearance of infection
Skin may appear normal initially, followed by swelling and ‘woody’ texture
Bronze-appearing skin with tense blebs/bullae, pallor, edema, areas of necrosis
Organisms
Usually Staphylococcus aureus; occasionally other microbes Imaging with CT scan or MRI; drainage to establish organism
Clostridium spp, usually C. perfringens or C. septicum Surgical exploration; cultures show clostridia
Drainage via CT-guided catheter or open procedure; intravenous antibiotics to cover S. aureus, and possibly other organisms, depending on host
Debridement; penicillin G and clindamycin intravenously
Diagnosis
Treatment
CT scan or MRI to define location of involvement; surgical exploration with cultures Debridement; penicillin G and clindamycin intravenously
Moderate Less acute than for gas gangrene, 3e4 days
Only late in the disease course Occurs late Moderate Usually absent Slight, sour smell Erythema
Streptococci and/or S. aureus Debridement with culture
Penicillin; antistaphylococcal coverage when S. aureus is isolated
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hosts. The exact therapy is tailored on the basis of the results of blood and wound culture. For example, with group A streptococci, the combination of penicillin and clindamycin is advocated. The length of therapy depends on the extent of disease, response to therapy, and the immune status of the host. Most patients require 3e4 weeks of therapy, with initial treatment via intravenous antibiotics. The prognosis is excellent, with the exception of cases discovered in the final stage with shock and multiorgan failure. PSOAS ABSCESS Although this infection is similar to pyomyositis given the development of an abscess or phlegmon within the psoas muscle, it differs in that most occur due to the spread of infection from a nearby site such as from a gastrointestinal source (malignancy, Crohn’s disease, appendicitis, diverticulitis) or an adjacent vertebral osteomyelitis usually due to S. aureus or M. tuberculosis.38 Other inciting events may be a complication of pregnancy or abortion in women, a retroperitoneal hematoma, or, rarely, hematogenous spread.39 Manifestations include lower abdominal or back pain, fevers, limping, and a positive psoas sign on examination.40 The diagnosis is usually established by CT scan imaging.41 The organism involved depends on the inciting event; in the case of a gastrointestinal disorder the infection is often polymicrobial involving aerobic and anaerobic bowel flora; S. aureus is frequently the cause when there is concurrent vertebral osteomyelitis or hematogenous seeding. M. tuberculosis may also involve the psoas muscle via extension from vertebral disease (Pott’s disease).40 Therapy is similar to that of pyomyositis, with surgical drainage and antibiotic therapy. Percutaneous drainage has been advocated since it is less invasive.40 For cases involving the gastrointestinal tract, a broad-spectrum antibiotic (with gram-positive and gram-negative coverage as well as anaerobic coverage) should be utilized. For primary psoas abscess, treatment should be primarily focused against S. aureus. Patients are usually followed clinically and with repeat imaging to assure resolution. The prognosis is favorable. GAS GANGRENE Gas gangrene is a rapidly progressive infection of the skeletal muscle(s) with necrosis and the potential for systemic toxicity. This infection may occur in association with a dirty wound after trauma or surgery and is usually due to Clostridium perfringens. Clinical scenarios include unclean traumatic wounds contaminated with soil (e.g. war wounds), wounds associated with gastrointestinal surgeries (e.g. bowel and biliary), septic abortions, injection sites, or trauma to an area with an inadequate blood supply. Devitalized tissue is a key characteristic for the development of gas gangrene. The other form of this infection develops in the absence of a wound and is due to bacteremia caused by Clostridium septicum, which usually occurs in association with an underlying gastrointestinal process such as carcinoma or neutropenic colitis.42 Occasionally, these infections are associated with seemingly uncomplicated gastrointestinal surgeries.43 Finally, C. novyi and other species of clostridia account for a small percentage of cases of gas gangrene. The pathogenesis of this infection includes rapid tissue necrosis manifesting as swelling, pallor, lack of bleeding, and loss of elasticity. The most important toxin mediating these effects is the phospholipase C (a-toxin); this toxin is responsible
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for the myonecrosis by splitting lecithin (the major phospholipid in cell membranes) and for the inhibition of the influx of leukocytes into the wound.44 The clinical presentation of this infection is rapid, occurring from 6 hours to 21 days (mean 3 days) after the injury. Pain is the key symptom and is usually severe in nature. The wound is edematous, tense, and has a foul odor. Tense blebs may appear in the overlying skin, and gas bubbles may emit from the wound. Palpation often reveals crepitus. Although gas is a key feature of this infection, it may occur late in the disease course, and its absence cannot rule out gas gangrene. The patient is usually febrile and visibly uncomfortable with vital signs consistent with shock (Table 4). Laboratory values often show leukocytosis; anemia may be present due to clostridium’s ability to cause hemolysis. Blood cultures are positive in 15% of cases. The diagnosis is typically made by demonstrating myonecrosis at surgery and having a positive culture for the organism. The gram stain shows a paucity of white blood cells in the wound as well as gram-positive bacilli with the classic boxcar shape. Imaging of the area should not delay surgical exploration; if a CT scan is performed, it may reveal muscle involvement including gas formation. Treatment consists of rapid surgical exploration both to establish the diagnosis and to widely debride the area of infection. Fasciotomies and/or amputation may be necessary. Antibiotics include a combination of penicillin G 24 million units daily in divided doses (with normal kidney function) and clindamycin 900 mg three times daily.45,46 No consensus exists for the use of hyperbaric oxygen therapy; the reasoning for its use includes increasing the local oxygen concentration to inhibit clostridial growth and toxin production.47,48 Perhaps its best use is in a setting where devitalized tissue cannot be adequately removed, as in the setting of involvement of the abdominal wall or paraspinal areas.15 Novel surgical and pharmaceutical strategies are needed to improve the outcome of this infection. The prognosis remains unsatisfactory, with mortality rates of 20e25%; those who survive may have disfiguring surgical wounds.49 Other forms of pyogenic myositis which are not due to clostridia include group A streptococcal necrotizing myositis, anaerobic streptococcal gangrene, and synergistic non-clostridial myonecrosis. Group A streptococcal necrotizing myositis Group A streptococcus is a common cause of cellulitis and soft-tissue infections, including abscess formation. Rarely, it manifests as severe myositis, termed group A streptococcal ‘necrotizing myositis’, ‘streptococcal myonecrosis’, or ‘gangrenous myositis’.50 The myositis may occur concurrently with necrotizing fasciitis and/or a toxicshock-like syndrome.51 Most patients developing gas necrotizing myositis had no underlying medical conditions, most were male (2:1 ratio) and younger than 50 years of age.50,51 The disease usually occurs spontaneously, a minority of cases occurring with a history of minor trauma. The clinical presentation consists of severe pain, usually occurring in an extremity (typically the leg), with fever, edema, and sometimes overlying skin findings (Table 4). The disease can be separated into three stages: (1) a prodromal stage with a nonspecific ‘flu-like’ illness including sore throat, a scarletinaform rash, and muscle pain lasting for 3e7 days; (2) a rapid intermediate phase with sudden escalation of the muscle pain over a period of hours; and (3) a late stage with manifestations of bacteremia, toxic shock, multiorgan failure, and/or compartment syndrome accompanying the myositis.
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The diagnosis is suspected on the basis of the clinical presentation. Differentiating myositis from necrotizing fasciitis is difficult, and these entities may occur concurrently. MRI imaging can define the exact location of involvement, but should not delay the need for surgical exploration, which is the gold standard for establishing the diagnosis. Necrotizing fasciitis commonly presents with violaceous bullae on the overlying skin and may help to differentiate these conditions.15 Clostridial myonecrosis is suggested by gas in the tissues. However, neither of these findings is absolute, and the diagnosis rests on findings on surgical exploration and microbiological culture. Laboratory findings are non-specific and usually include leukocytosis and an elevated creatine phosphokinase level; some cases have a normal white blood count and erythrocyte sedimentation rate (ESR) due to the rapid speed of the infection and lack of time for a sufficient immune response to develop.52 Treatment consists of immediate surgical debridement and reassessment of the tissues to evaluate the need for further removal of devitalized tissues. For group A streptococci, the antibiotics of choice include intravenous penicillin G (24 million units daily in divided doses) and clindamycin, 900 mg three times daily; the latter is utilized due to the ‘Eagle effect’ since this antibiotic has good activity against the bacteria in the stationary phase of growth and inhibits toxin production.53 Intravenous immunoglobulin may also be beneficial in cases of toxic shock associated with group A streptococci.54 Research efforts in the area of novel antimicrobial, antitoxin, or immune-regulator medications are needed. Prognosis is guarded, especially in the presence of toxemia, with mortality rates of 30e85%.50,51,55 Improvement in the outcome depends on the rapid recognition of the condition, immediate therapy, and the development of novel treatment strategies.
Anaerobic streptococcal myonecrosis This clinical entity bears similarities to gas gangrene, as it usually occurs in association with a wound, often after trauma, and gas may be present within the tissues. Differentiating findings between the two clinical entities include the absence of early severe pain associated with the wound and the presence of early erythema. Like gas gangrene, the wound commonly has a foul odor (Table 4). The causal agents are typically mixtures of streptococci (group A and anaerobic) and/or S. aureus. Treatment is with surgical debridement and antibiotics. If streptococci alone are present, penicillin is adequate. With the presence of other organisms such as staphylococci additional agents are employed since most staphylococci (>95%) are resistant to penicillin alone.
OTHER FORMS OF BACTERIAL MYONECROSIS Synergistic non-clostridial myonecrosis may occur among patients with vascular insufficiency (e.g. diabetes mellitus, cardiorenal disease, obesity) or among neutropenic patients. This infection involves the skin, subcutaneous tissues, fascia, and muscle; it is usually polymicrobial, with both aerobic and anaerobic pathogens. Similar infections can involve patients with vascular grafts with a variety of organisms, including Bacillus.56 Patients with wounds and exposure to fresh water may develop infection with Aeromonas.57
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MYALGIAS ASSOCIATED WITH EOSINOPHILIA Infectious myositis accompanied by eosinophilia is typically due to a parasitic infection. These disorders characteristically manifest as diffuse myalgias, although specific muscles may be most involved. Trichinosis Trichinosis occurs after the ingestion of insufficiently cooked meat that is contaminated with the parasite Trichinella (most commonly T. spiralis). Generally, the meat involved is pork, although a rising number of cases associated with wild meat e including bear, walrus, seal, cougar, and wild boar e have been reported.58 Patients may develop symptoms 1e2 weeks after ingestion; some infections are subclinical, depending on the size of the inoculum. After ingestion, larvae penetrate the wall of the small intestine of the human and disseminate throughout the body via the bloodstream. The earliest symptoms may include gastrointestinal discomfort, diarrhea, and vomiting. Muscle soreness and weakness may occur as larvae become encapsulated in the muscles; the most common sites include the diaphragm, extraocular, masseter, and tongue muscles, but other sites may be involved. In addition, classic findings include fever, edema of the upper eyelids, subconjunctival hemorrhages, eye pain, and prostration. Complications of trichinosis include both neurological and cardiac involvement due to the deposition of larvae in these areas.14 Laboratory testing shows eosinophilia; an elevated creatine phosphokinase level suggests extensive muscular involvement. The diagnosis is typically established by the classic symptoms of trichinosis along with the food ingestion history. Biopsy of skeletal muscle can show the encysted larvae but is typically not required. Serologic tests, such as the enzyme-linked immunofluorescence assay and the bentonite flocculation assay, are the most common methods for confirming the diagnosis. Of note, these tests usually do not turn positive for 3 or more weeks after infection. The main disease in the differential diagnosis of trichinosis is the eosinophiliaemyalgia syndrome which generally occurs after ingestion of tryptophan. Treatment is with albendazole or mebendazole. These drugs are most beneficial in the early course of the disease since they act at the gastrointestinal stage but have little activity against larvae embedded within the musculature.59 Better antiparasitic drugs with penetration into the muscles are needed to treat myositis. Bed rest and salicylates may be useful. Corticosteroids are reserved for life-threatening disease, including brain or heart involvement; patients with active myositis may also symptomatically improve with steroids in doses of 30e80 mg daily. Disease prevention includes ensuring that meat is adequately cooked (55 C), frozen (25 C for 10 or more days), or irradiated to kill the larvae. Cysticercosis Cysticercosis results from the ingestion of undercooked pork contaminated with Taenia solium eggs; in addition, patients may become infected by ingestion of other food products or water contaminated with eggs. Similarly to trichinosis, the disease disseminates from the upper gastrointestinal tract to the skeletal muscles, central nervous system, heart, and eye. Incubation period is from weeks to years. Muscular symptoms of this infection are uncommon, but myalgias, fever, and eosinophilia may occur. The most
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significant presentation of this disease is the neurological manifestations resulting from the deposition of the organism, including seizures, headaches, or psychiatric disturbances. The diagnosis of muscular involvement is most commonly made when radiological films show calcified cysts (‘puffed rice’ appearance) in the muscles. Occasionally, palpation of the musculature may reveal ‘oval swellings’ between the fibers. Rarely, pseudohypertrophy of the muscles (especially the calves and thighs) can occur with widely disseminated disease.60 Serologic tests are available to confirm the diagnosis. Treatment is praziquantel for intestinal disease. For central nervous system disease, praziquantel or albendazole may be utilized, but care must be taken due to the risk of increasing edema due to cyst death; often, corticosteroids are employed. Infectious disease and neurosurgical consultations should be obtained in these cases. Other parasitic infections Acute schistosomiasis (Katayama syndrome) may manifest as fevers, myalgias, and eosinophilia, as well as abdominal pain, headaches, and diarrhea. This syndrome occurs 2e8 weeks after exposure to the cercariae, which penetrate the skin after exposure to contaminated fresh water in endemic areas, including Africa, the Middle East, Southeast Asia, South America, and Central America. Myalgias may also occur during the acute phase of Chaga’s disease (Trypanosoma cruzi), along with periophthalmic edema (Romana’s sign), fever, headaches, and adenopathy after the bite of a triatomine bug in South or Central America. Toxocariasis, the cause of visceral larva migrans, may rarely present with muscle pain in association with eosinophilia.
Practice points infectious myositis may be caused by viral, bacterial, fungal, or parasitic pathogens pyogenic myositis is classified as clostridial myonecrosis (gas gangrene), group A streptococcus necrotizing myositis, or non-clostridial myositis such as anaerobic streptococcal myonecrosis pyomyositis is an intramuscular infection involving one or more of the skeletal muscle groups and is the result of transient bacteremia not spread from a contiguous site the most common organism associated with pyomyositis is Staphylococcus aureus treatment of pyomyositis consists of drainage, frequently using CT guidance, and intravenous antibiotics psoas abscess usually develops in association with a gastrointestinal disorder or an adjacent vertebral osteomyelitis gas gangrene is a rapidly progressive infection of the skeletal muscle(s) with necrosis and often gas formation the cause of gas gangrene is usually Clostridium perfringens associated with contaminated wounds due to trauma or surgical sites; Clostridium septicum may be implicated in association with a gastrointestinal malignancy
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treatment of gas gangrene and group A streptococcal myositis consists of rapid surgical exploration and debridement, as well as intravenous penicillin G and clindamycin hyperbaric oxygen therapy can be considered in cases of gas gangrene, but there is no clear consensus on its benefit group A streptococcus necrotizing myositis presents with severe pain, usually occurring in the extremity, fever, edema, and sometimes a toxic-shock-like syndrome non-clostridial myonecrosis includes anaerobic streptococcal myonecrosis, synergistic non-clostridial myonecrosis, myositis associated with vascular grafts, and myositis associated with freshwater exposure (Aeromonas) parasitic infections may manifest as myositis with eosinophilia trichinosis develops after ingestion of contaminated pork or wild meat classic findings of trichinosis include fever, edema of the upper eyelids, subconjunctival hemorrhages, and muscle discomfort cysticercosis involvement of the musculature is most commonly recognized on radiologic films showing calcified cysts (‘puffed rice’ appearance)
Research agenda novel diagnostic tests to determine the etiology of myositis, including molecular tools e polymerase chain reaction (PCR), DNA analysis e are needed given the high mortality rates of gas gangrene and group A streptococcal myonecrosis, improved therapies for these conditions, including novel pharmaceutical medications, anti-toxins, and/or immune regulators controlled studies are needed to determine the efficacy of hyperbaric oxygen in cases of gas gangrene treatments which are more effective in treating Trichinella in the muscle compartments and cysticercosis would be beneficial
DISCLAIMER The views expressed in this article are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. REFERENCES *1. Wortmann RL. Inflammatory diseases of muscle and other myopathies. In Harris E, Budd R et al (eds.) Kelley’s Textbook of Rheumatology. 7th edn. Philadelphia: Saunders Elsevier, 2005, pp. 1309e1335. 2. Christopher-Stine L & Plotz PH. Myositis: an update on pathogenesis. Current Opinion in Rheumatology 2004; 16: 700e706.
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*3. Wadia NH & Katrak SM. Muscle infection: viral, parasitic, bacterial, and spirochetal. In Schapira AHV & Griggs RC (eds.) Muscle Diseases. 1st edn. Boston: Butterworth Heinemann, 1999, pp. 339e362. 4. Daley AJ, Atkinson M & Nallusamy R. Group A streptococcal myositis. Journal of Paediatrics and Child Health 1999; 35: 588e590. 5. Ichinose K, Migita K, Sekita T et al. Parvovirus B19 infection and myofasciitis. Clinical Rheumatology 2004; 23: 184e185. 6. Eliasson H & Back E. Myositis and septicaemai caused by Francisella tularensis biovar holarctica. Scandinavian Journal of Infectious Diseases 2003; 5: 510e511. 7. Wang JY, Lee LN, Hsueh PR et al. Tuberculous myositis: a rare but existing clinical entity. Rheumatology 2003; 42: 836e840. 8. Sharma M, Khatib R, Jones BA & Fakih MG. Cryptococcus neoformans myositis without dissemination. Scandinavian Journal of Infectious Diseases 2002; 34: 858e859. 9. Behar DM & Ben-Ami H. Myositis accompanying Rickettsia conorii infection. The Israel Medical Association Journal 2001; 3: 471e472. 10. Field AS, Marriott DJ, Milliken ST et al. Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patient with AIDS. Journal of Clinical Microbiology 1996; 34: 2803e2811. 11. Gave AA, Torres R & Kaplan L. Cryptococcal myositis and vasculitis: an unusual necrotizing soft tissue infection. Surgical Infections 2004; 5: 309e313. 12. Agyeman P, Duppenthaler A, Heininger U & Aebi C. Influenza-associated myositis in children. Infection 2004; 32: 199e203. 13. Behan WM, Behan PO, Draper IT & Williams H. Does Toxoplasma cause polymyositis? Report of a case of polymyositis associated with toxoplasmosis and a critical review of the literature. Acta Neuropathologica 1983; 61: 246e252. 14. Capo V & Despommier DD. Clinical aspects of infection with Trichinella spp. Clinical Microbiology Reviews 1996; 9: 47e54. *15. Pasternack MS & Swartz MN. Myositis. In Mandel GL, Bennett JE & Dolin RD (eds.) Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 6th edn. New York: Elsevier/Churchill Livingstone, 2005, pp. 1194e1204. 16. Reimers CD, de Koning J, Neubert U et al. Borrelia burgdorferi myositis: report of eight patients. Journal of Neurology 1993; 240: 278e283. 17. Smith RD, Konoplev S, DeCourten-Myers G & Brown T. West Nile virus encephalitis with myositis and orchitis. Human Pathology 2004; 35: 254e258. *18. Brook I. Microbiology and management of myositis. International Orthopaedics 2004; 28: 257e260. 19. Hu JJ, Kao CL, Lee PI et al. Clinical features of influenza A and B in children and association with myositis. Journal of Microbiology, Immunology, and Infection 2004; 37: 95e98. 20. Plonquet A, Bassez G, Authier FJ et al. Toxoplasmic myositis as a presenting manifestation of idiopathic CD4 lymphocytopenia. Muscle Nerve 2003; 27: 761e765. 21. Solomon T, Ooi MH, Beasley DW & Mallewa M. West Nile encephalitis. British Medical Journal 2003; 326: 865e869. 22. Horn CV & Master S. Pyomyositis tropicans in Uganda. East African Medical Journal 1968; 45: 463e471. 23. Ansaloni L. Tropical pyomyositis. World Journal of Surgery 1996; 20: 613e617. 24. Chiedozi LC. Pyomyositis. Review of 205 cases in 112 patients. American Journal of Surgery 1979; 137: 255e259. 25. O’Neill DS, Baquis G & Moral L. Infectious myositis: a tropical disease steals out of its zone. Postgraduate Medicine 1996; 100: 193e194, 199e200. *26. Crum NF. Bacterial pyomyositis in the United States. American Journal of Medicine 2004; 117: 420e428. 27. Fowler A & Mackay A. Community-acquired methicillin-resistant Staphylococcus aureus pyomyositis in an intravenous drug user. Journal of Medical Microbiology 2006; 55: 123e125. 28. Miyake H. Beitrage (Beitraege) zur Kenntnis der sogenannten Myositis Infectiosa. Mitteilungen aus den Grenzgebieten der Medizin und Chirurgie 1904; 13: 155e198. 29. Smith IM & Vickers AB. Natural history of 338 treated and untreated patients with staphylococcal septicaemia (1936e1955). Lancet 1960; 1: 1318e1322. 30. Schwartzman WA, Lambertus MW, Kennedy CA & Goetz MB. Staphylococcal pyomyositis in patients infected by the human immunodeficiency virus. American Journal of Medicine 1991; 90: 595e600.
1096 N. F. Crum-Cianflone 31. Widrow CA, Kellie SM, Saltzman BR & Mathur-Wagh U. Pyomyositis in patients with the human immunodeficiency virus: an unusual form of disseminated bacterial infection. American Journal of Medicine 1991; 91: 129e136. 32. Chen W-S & Wan Y-L. Iliacus pyomyositis mimicking septic arthritis of the hip joint. Archives of Orthopaedic and Trauma Surgery 1996; 115: 233e235. 33. Chusid MJ, Hill WC, Bevan JA & Sty JR. Proteus pyomyositis of the piriformis muscle in a swimmer. Clinical Infectious Diseases 1998; 26: 194e195. 34. Wysoki MG, Angeid-Backman E & Izes BA. Iliopsoas myositis mimicking appendicitis: MRI diagnosis. Skeletal Radiology 1997; 26: 316e318. 35. Walji S, Rubenstein J, Shannon P & Carette S. Disseminated pyomyositis mimicking idiopathic inflammatory myopathy. The Journal of Rheumatology 2005; 32: 184e187. 36. Ruiz ME, Yohannes S & Wladyka CG. Pyomyositis caused by methicillin-resistant Staphylococcus aureus. New England Journal of Medicine 2005; 352: 1488e1489. *37. Small LN & Ross JJ. Tropical and temperate pyomyositis. Infectious Disease Clinics of North America 2005; 19: 981e989. 38. Van den Berge M, de Marie S, Kuipers T et al. Psoas abscess: report of a series and review of the literature. The Netherlands Journal of Medicine 2005; 63: 413e416. 39. Agrawal SN, Dwivedi AJ & Khan M. Primary psoas abscess. Digestive Diseases and Sciences 2002; 47: 2103e2105. *40. Mallick IH, Thoufeeq MH & Rajendran TP. Iliopsoas abscesses. Postgraduate Medical Journal 2004; 80: 459e462. 41. Gordin F, Stamler C & Mills J. Pyogenic psoas abscesses: noninvasive diagnostic techniques and review of the literature. Reviews of Infectious Diseases 1983; 5: 1003e1011. 42. El-Masry S. Spontaneous gas gangrene associated with occult carcinoma of the colon: a case report and review of the literature. International Surgery 2005; 90: 245e247. 43. Boenicke L, Maier M, Merger M et al. Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel perforation in an otherwise healthy individual: report of a case. Langenbeck’s Archives of Surgery 2006; 391: 157e160. 44. Kennedy CL, Krejany EO, Young LF et al. The alpha-toxin of Clostridium septicum is essential for virulence. Molecular Microbiology 2005; 57: 1357e1366. 45. Stevens DL, Maier KA & Mitten JE. Effect of antibiotics on toxin production and viability of Clostridium perfringens. Antimicrobial Agents and Chemotherapy 1987; 31: 213e218. 46. Stevens DL, Laine BM & Mitten JE. Comparison of single and combination antimicrobial agents for prevention of experimental gas gangrene cause by Clostridium perfringens. Antimicrobial Agents and Chemotherapy 1987; 31: 312e316. 47. Stevens DL, Bryant AE, Adams K & Mader JT. Evaluation of therapy with hyperbaric oxygen for experimental infection with Clostridium perfringens. Clinical Infectious Diseases 1993; 17: 231e237. 48. Wang C, Schwaitzberg S, Berliner E et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Archives of Surgery 2003; 138: 272e279. *49. Hart GB, Lamb RC & Strauss MB. Gas gangrene. The Journal of Trauma 1983; 23: 991e1000. *50. Subramanian KN & Lam KS. Malignant necrotizing streptococcal myositis: a rare and fatal condition. The Journal of Bone and Joint Surgery. British Volume 2003; 85: 277e278. *51. Stevens DL, Tanner MH, Winship J et al. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. New England Journal of Medicine 1989; 321: 1e7. 52. Adams EM, Gudmundsson S, Yocum DE et al. Streptococcal myositis. Archives of Internal Medicine 1985; 145: 1020e1023. 53. Stevens DL, Gibbons AE, Bergstrom R & Winn V. The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. The Journal of Infectious Diseases 1988; 158: 23e28. 54. Darenberg J, Ihendyane N, Sjolin J et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial. Clinical Infectious Diseases 2003; 37: 333e340. 55. Jahnson L, Berggren L, Bjorsell-Ostling E et al. Streptococcal myositis. Scandinavian Journal of Infectious Diseases 1992; 24: 661e665.
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56. Johnson DA, Aulicino PL & Newby JG. Bacillus cereus-induced myonecrosis. The Journal of Trauma 1984; 24: 267e270. 57. Heckerling PS, Stine TM, Pottage JC et al. Aeromonas hydrophilia myonecrosis and gas gangrene in a nonimmunocompromised host. Archives of Internal Medicine 1983; 143: 2005e2007. 58. Pozio E. New patterns of Trichinella infection. Veterinary Parasitology 2001; 98: 133e148. 59. Pozio E, Sacchini D, Sacchi L et al. Failure of mebendazole in the treatment of humans with Trichinella spiralis infection at the stage of encapsulating larvae. Clinical Infectious Diseases 2001; 32: 638e642. 60. Wadia NH. Dissemianted cystericercosis: pseudohypertrophic muscular type. In Rose CF (ed.) Recent Advances in Tropical Neurology. 1st edn. Amsterdam: Elsevier, 1995, pp. 119e130.
4 Infectious myositis Nancy F. Crum-Cianflone*
MD, MPH, FACP
Staff, Infectious Disease Physician Infectious Disease Division, Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, CA 92134-1005, USA
Infectious myositis, an infection of the skeletal muscle(s), is uncommon. This clinical entity may be caused by viral, bacterial, fungal, and parasitic pathogens. Viral etiologies typically cause diffuse myalgias and/or myositis, whereas bacteria and fungi usually lead to a local myositis which may be associated with sites compromised by trauma or surgery and are more common among immunocompromised patients. Localized collections within the muscles are referred to as pyomyositis. Other pyogenic causes of myositis include gas gangrene, group A streptococcal myonecrosis, and other types of non-clostridial myonecrosis. Early recognition and treatment of these conditions are necessary as they may rapidly become life-threatening. Key words: myositis; pyomyositis; psoas abscess; group A streptococcus; Clostridium spp; trichinosis.
Myositis refers to inflammation of the muscles and may be due to infectious and noninfectious etiologies. This paper focuses on the infectious causes of myositis. Noninfectious etiologies include a broad range of clinical conditions, including idiopathic inflammatory myopathies (e.g. polymyositis) and myopathies associated with autoimmune disorders, medications, genetic disorders, endocrine diseases, and electrolyte disturbances (Table 1).1 Some non-infectious myopathies may be triggered by environmental agents, including microorganisms.2 For example, polymyositis may be triggered in genetically predisposed individuals by viruses such as coxsackievirus B1, human immunodeficiency virus (HIV), human T-lymphotrophic virus 1 (HTLV-1), hepatitis B, influenza, adenovirus, and echovirus. INFECTIOUS MYOSITIS The infectious causes of myositis, summarized in Table 2, include viral, bacterial, fungal, and parasitic pathogens.1,3e17 Some infections cause focal myositis, while others lead * Tel.: þ1 619 532 8134/40; Fax: þ1 619 532 8137. E-mail address: [email protected] 1521-6942/$ - see front matter ª 2006 Published by Elsevier Ltd.
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Table 1. Non-infectious etiologies of myositis. Idiopathic inflammatory myopathies Polymyositis Dermatomyositis Myositis associated with collagen vascular diseases Polyarteritis nodosum Wegener’s granulomatosis Systemic lupus erythematosus Sjogren’s syndrome Rheumatoid arthritis Scleroderma Polymyalgia rheumatica Mixed connective tissue disease Adult Still’s disease Vasculitis e leukocytoclastic, hypersensitivity Myositis associated with malignancies Inclusion body myositis Other forms of inflammatory myopathies Myositis associated with eosinophilia Myositis ossificans Giant-cell myositis Myopathies caused by medications and toxins Metabolic myopathies Disorders in glycogen metabolism Endocrine disorders Electrolyte abnormalities Nutritional Disease which may cause myopathic symptoms Neuropathic disorders Muscular dystrophies Others including diseases of the neuromuscular junction Medication-related adverse events
to diffuse involvement of the musculature (Table 3). Bacteria and fungi usually present as a focal myositis, whereas viral and parasitic pathogens are more likely to present as a diffuse myositis. Further, bacterial myositis may occur in association with areas of the body that have been injured or compromised by trauma, surgery, the presence of a foreign body, or ischemia. In addition, hosts that are immunocompromised have a higher risk of many types of myositis, including bacterial and fungal. Bacteria and other microorganisms may cause focal infections in the musculature such as with pyomyositis or psoas abscesses. Pyogenic myositis is classified as clostridial myonecrosis (gas gangrene), group A streptococcus necrotizing myositis, or a non-clostridial myositis such as anaerobic streptococcal myonecrosis.18 Certain infectious diseases can be associated with myalgias, with or without myositis, including e.g. influenza, dengue, Rocky Mountain spotted fever (Rickettsia rickettsii), infective endocarditis, Lyme disease (Borrelia burgdorferi), toxoplasmosis, HIV infection, HTLV-1, and other virus diseases (see Table 2). Influenza virus, especially B, may manifest as myositis, which typically affects the bilateral lower calves; cases of rhabdomyolysis have been described.12,19 Myalgias accompany endocarditis in
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Table 2. Infectious causes of myositis and/or myalgias. Viral: Adenovirus Coxsackieviruses, especially B Cytomegalovirus (CMV) Echovirus EpsteineBarr virus (EBV) Hepatitis B virus Human immunodeficiency virus (HIV) Human T-cell lymphotrophic virus type 1 (HTLV-1) Influenza virus Mumps virus Parvovirus Rubella virus Varicellaezoster virus (VZV) West Nile Virus (WNV) Bacterial Staphylococcus Streptococcus Gram-negative organisms: Enterobacteria (including Yersinia), Pseudomonas, Aeromonas, others Anaerobes: Clostridium, Bacteroides, Fusobacterium, Peptostreptococcus, others ‘Atypical bacteria’ Bartonella Borrelia burgdorferi (Lyme disease) Francisella tularensis Leptospira Mycobacteria tuberculosis and other species Mycoplasma pneumoniae Rickettsia (including Rocky Mountain spotted fever) Fungal Aspergillus Candida Cryptococcus Fusarium Pneumocystis Parasitic Echinococcus Microsporidia e Trachipleistophora, Pleistophora Schistosoma Spirometra mansonoides (sparganosis) Toxocara Toxoplasma Trichinella Trypanosoma cruzi
15% of cases and may be diffuse or focal.15 Lyme disease is associated with proximal muscle involvement; rarely orbital myositis may occur.16 Toxoplasmosis-associated myositis typically appears among immunocompromised patients, especially those with a low CD4 cell count, and resembles autoimmune polymyositis.13,20 The West
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Table 3. Classification of infectious myositis. Non-pyogenic, generalized: Myalgias Viruses: influenza, dengue, HIV infection, HTLV-1, hepatitis B, EpsteineBarr virus, cytomegalovirus Bacteria: Rocky Mountain spotted fever (Rickettsia rickettsii), infective endocarditis, Lyme disease (Borrelia burgdorferi) Parasitic: toxoplasmosis Pleurodynia Coxsackievirus B Myalgias with Trichinosis (Trichinella spiralis) eosinophilia Cysticercosis (Taenia solium) Other parasitic diseases Pyogenic, typically localized infection: Pyomyositis Usually Staphylococcus aureus; may involve streptococci (group A, B, C, G or S. pneumoniae), Gram-negative organisms, anaerobes, mycobacteria, fungi, or parasites. Psoas abscess Gram-negative bacilli, anaerobes, S. aureus, M. tuberculosis Gas gangrene Clostridium spp, usually C. perfringens, less frequently C. septicum and C. novyi Non-clostridial Group A streptococcal necrotizing myositis myositis Anaerobic streptococcal myonecrosis Other forms of bacterial myonecrosis
Nile Virus may also present with myalgias during the acute presentation of West Nile Fever; less than 1% of patients develop neurologic symptoms which may include acute flaccid paralysis due to involvement of the anterior horn of the spinal cord.17,21 Finally, coxsackievirus B may cause myalgias in the musculature of the rib cage referred to as the pleurodynia syndrome or Bornholm disease. Infections manifesting as myalgias occurring with eosinophilia are described below; they are parasitic in nature. PYOMYOSITIS Pyomyositis is an intramuscular infection which involves one or more of the skeletal muscle groups, and which is not a result of infection of adjacent skin, soft tissue, or bone (Table 3). It was originally described in the tropics, and originally named pyomyositis tropicans.22 In these areas, the pyomyositis accounts for 1e4% of hospitalizations and is often associated with trauma, nutritional deficiencies, and/or concomitant parasitic infections (e.g. migration of Toxocara or the guinea worm, Dracunculus).23,24 In the past few decades, cases have been increasingly described in the developed world, especially among immunocompromised people such as those with HIV infection, malignancies, rheumatologic conditions, or diabetes mellitus.25 A recent review described 84 cases among HIV-infected people.26 Intravenous drug users are also at heightened risk.27 The pathogenesis of pyomyositis involves the occurrence of transient bacteremia in the setting of muscular injury; the latter is necessary since the musculature is relatively resistant to infection, and although bacteremia is quite common, pyomyositis is not.28,29 Intensive exercise or local trauma have been suggested, but many patients do not have a consistent history.26 In addition to trauma, other factors may cause muscular injury, including concurrent medical conditions (e.g. HIV, diabetes mellitus) and medications (e.g. zidovudine, steroids). Patients with HIV have several risk factors
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for their increased susceptibility to developing pyomyositis, including HIV myopathy, drug-induced mitochondrial dysfunction, concurrent bacterial infections, high rates of S. aureus colonization, and impaired neutrophil function.30,31 Three stages of pyomyositis have been described. (1) The invasive stage involves infection of the muscle, which causes the muscle to become edematous and painful; aspiration is unrevealing at this stage since there is no focal collection. (2) The suppurative phase is characterized by formation of an abscess and usually occurs 1e3 weeks later, with aspiration revealing pus; most cases are diagnosed in this stage. (3) The last stage involves the systemic spread of the infection, leading to septicemia, multifocal abscesses, and shock.24 Presenting signs and symptoms during the first stage include localized pain, swelling, and fever. There is often no erythema or warmth of the overlying skin since the infection is deep within the muscle. As the abscess develops, increasing pain, swelling and a ‘woody’ texture to the overlying area (Table 4) may exist. Pyomyositis is frequently misdiagnosed in these early stages as a muscle strain, thrombosis, hematoma, septic arthritis, or osteomyelitis. Pyomyositis that involves the iliacus or the obturator internus may mimic septic arthritis of the hip; pyriformic pyomositis may simulate a spinal epidural abscess, and iliopsoas myositis may be confused with appendicitis.32e34 Among patients with HIV or other immunocompromising conditions, the presenting symptoms may be particularly subtle due to a poor host immune response to the infection. Typically, a single muscle group is involved; however, multifocal involvement is noted in approximately 20% of cases.26 Occasionally, cases present as a more diffuse process confused with idiopathic inflammatory myopathy or polymyositis.35 The most common locations include the large skeletal muscles of the lower extremities (especially the quadriceps femoris and gluteus group) and the trunk muscles. Regional adenitis is not found on examination. The diagnosis is established by radiological imaging of the area of infection by ultrasound, CT scan, or MRI. CT scanning is the most commonly employed since it provides good definition of the areas of involvement and is relatively quick. MRI provides the most precise imaging. Laboratory tests are non-specific; leukocytosis is typically present, but may be absent among neutropenic patients or those with endstage AIDS. The erythrocyte sedimentation rate is usually elevated. Eosinophilia may occur in tropical cases and usually reflects an underlying parasitic infection. Levels of creatine phosphokinase and aldolase are typically normal, despite muscular involvement by the infection. Blood cultures may be positive in 5e30% of cases, with higher rates of positivity in the developed world. The specific etiologic agent for pyomyositis is typically discovered at the time of drainage e most commonly via CT-guided aspiration or pigtail placement, or an open procedure. The most frequent organism is Staphylococcus aureus, accounting for up to 95% of tropical cases and approximately 70% of cases in the developed world. Recently, cases due to MRSA have been described.27,36 Several other microbes have also been described, including streptococci, gram-negative bacilli (including enteric organisms, Bartonella), anaerobes (Fusobacterium, Clostridium), mycobacteria (M. tuberculosis and M. avium complex), microsporidia (especially among AIDS patients), and fungi (Cryptococcus, Aspergillus, Pneumocystis carinii ( jiroveci), Candida, Fusarium).11,26,37 Anaerobes may be found when careful culture procedures are followed. Cases involving fungi or microsporidia usually occur among immunocompromised patients.10 Treatment usually consists of both antibiotics and surgical drainage; if the disease is recognized in stage 1, antibiotics alone are curative. Antibiotics should provide coverage against S. aureus, such as with a b-lactamase-resistant penicillin; among patients at risk for MRSA, vancomycin should be considered. Broad-spectrum agents with good gramnegative coverage should be contemplated, especially among immunocompromised
1088 N. F. Crum-Cianflone
Table 4. Clinical presentations and management of infectious myositis of various etiologies. Pyomyositis
Gas gangrene
Group A Anaerobic Streptococcal streptococcal Necrotizing Myositis myonecrosis
Predisposing Residence in a tropical condition(s) area; trauma; in the developed world: immunocompromising conditions (HIV, diabetes, cancer) Fever Moderate Onset Gradual
Local trauma or surgery; for Clostridium septicum, evaluate for underlying gastrointestinal disorder Moderate to high Acute with a 2e3-day incubation period
Often no underlying Local trauma medical conditions among the patients; may be related to minor trauma
Systemic toxicity
Significant
Minimal; sepsis may develop in the last stage of infection Pain Localized, moderate Swelling Minimal to moderate Crepitus/gas Absent in tissues Odor None
Early, severe Significant Present
Moderate to high May have a prodromal phase, followed by an acute presentation with increasing muscular symptoms May be associated with toxic shock-like syndrome Severe Significant Absent
Foul-smelling
None Uninvolved overlying skin to a violaceous appearance with bullae especially with concurrent necrotizing fasciitis Group A streptococcus
Appearance of infection
Skin may appear normal initially, followed by swelling and ‘woody’ texture
Bronze-appearing skin with tense blebs/bullae, pallor, edema, areas of necrosis
Organisms
Usually Staphylococcus aureus; occasionally other microbes Imaging with CT scan or MRI; drainage to establish organism
Clostridium spp, usually C. perfringens or C. septicum Surgical exploration; cultures show clostridia
Drainage via CT-guided catheter or open procedure; intravenous antibiotics to cover S. aureus, and possibly other organisms, depending on host
Debridement; penicillin G and clindamycin intravenously
Diagnosis
Treatment
CT scan or MRI to define location of involvement; surgical exploration with cultures Debridement; penicillin G and clindamycin intravenously
Moderate Less acute than for gas gangrene, 3e4 days
Only late in the disease course Occurs late Moderate Usually absent Slight, sour smell Erythema
Streptococci and/or S. aureus Debridement with culture
Penicillin; antistaphylococcal coverage when S. aureus is isolated
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hosts. The exact therapy is tailored on the basis of the results of blood and wound culture. For example, with group A streptococci, the combination of penicillin and clindamycin is advocated. The length of therapy depends on the extent of disease, response to therapy, and the immune status of the host. Most patients require 3e4 weeks of therapy, with initial treatment via intravenous antibiotics. The prognosis is excellent, with the exception of cases discovered in the final stage with shock and multiorgan failure. PSOAS ABSCESS Although this infection is similar to pyomyositis given the development of an abscess or phlegmon within the psoas muscle, it differs in that most occur due to the spread of infection from a nearby site such as from a gastrointestinal source (malignancy, Crohn’s disease, appendicitis, diverticulitis) or an adjacent vertebral osteomyelitis usually due to S. aureus or M. tuberculosis.38 Other inciting events may be a complication of pregnancy or abortion in women, a retroperitoneal hematoma, or, rarely, hematogenous spread.39 Manifestations include lower abdominal or back pain, fevers, limping, and a positive psoas sign on examination.40 The diagnosis is usually established by CT scan imaging.41 The organism involved depends on the inciting event; in the case of a gastrointestinal disorder the infection is often polymicrobial involving aerobic and anaerobic bowel flora; S. aureus is frequently the cause when there is concurrent vertebral osteomyelitis or hematogenous seeding. M. tuberculosis may also involve the psoas muscle via extension from vertebral disease (Pott’s disease).40 Therapy is similar to that of pyomyositis, with surgical drainage and antibiotic therapy. Percutaneous drainage has been advocated since it is less invasive.40 For cases involving the gastrointestinal tract, a broad-spectrum antibiotic (with gram-positive and gram-negative coverage as well as anaerobic coverage) should be utilized. For primary psoas abscess, treatment should be primarily focused against S. aureus. Patients are usually followed clinically and with repeat imaging to assure resolution. The prognosis is favorable. GAS GANGRENE Gas gangrene is a rapidly progressive infection of the skeletal muscle(s) with necrosis and the potential for systemic toxicity. This infection may occur in association with a dirty wound after trauma or surgery and is usually due to Clostridium perfringens. Clinical scenarios include unclean traumatic wounds contaminated with soil (e.g. war wounds), wounds associated with gastrointestinal surgeries (e.g. bowel and biliary), septic abortions, injection sites, or trauma to an area with an inadequate blood supply. Devitalized tissue is a key characteristic for the development of gas gangrene. The other form of this infection develops in the absence of a wound and is due to bacteremia caused by Clostridium septicum, which usually occurs in association with an underlying gastrointestinal process such as carcinoma or neutropenic colitis.42 Occasionally, these infections are associated with seemingly uncomplicated gastrointestinal surgeries.43 Finally, C. novyi and other species of clostridia account for a small percentage of cases of gas gangrene. The pathogenesis of this infection includes rapid tissue necrosis manifesting as swelling, pallor, lack of bleeding, and loss of elasticity. The most important toxin mediating these effects is the phospholipase C (a-toxin); this toxin is responsible
1090 N. F. Crum-Cianflone
for the myonecrosis by splitting lecithin (the major phospholipid in cell membranes) and for the inhibition of the influx of leukocytes into the wound.44 The clinical presentation of this infection is rapid, occurring from 6 hours to 21 days (mean 3 days) after the injury. Pain is the key symptom and is usually severe in nature. The wound is edematous, tense, and has a foul odor. Tense blebs may appear in the overlying skin, and gas bubbles may emit from the wound. Palpation often reveals crepitus. Although gas is a key feature of this infection, it may occur late in the disease course, and its absence cannot rule out gas gangrene. The patient is usually febrile and visibly uncomfortable with vital signs consistent with shock (Table 4). Laboratory values often show leukocytosis; anemia may be present due to clostridium’s ability to cause hemolysis. Blood cultures are positive in 15% of cases. The diagnosis is typically made by demonstrating myonecrosis at surgery and having a positive culture for the organism. The gram stain shows a paucity of white blood cells in the wound as well as gram-positive bacilli with the classic boxcar shape. Imaging of the area should not delay surgical exploration; if a CT scan is performed, it may reveal muscle involvement including gas formation. Treatment consists of rapid surgical exploration both to establish the diagnosis and to widely debride the area of infection. Fasciotomies and/or amputation may be necessary. Antibiotics include a combination of penicillin G 24 million units daily in divided doses (with normal kidney function) and clindamycin 900 mg three times daily.45,46 No consensus exists for the use of hyperbaric oxygen therapy; the reasoning for its use includes increasing the local oxygen concentration to inhibit clostridial growth and toxin production.47,48 Perhaps its best use is in a setting where devitalized tissue cannot be adequately removed, as in the setting of involvement of the abdominal wall or paraspinal areas.15 Novel surgical and pharmaceutical strategies are needed to improve the outcome of this infection. The prognosis remains unsatisfactory, with mortality rates of 20e25%; those who survive may have disfiguring surgical wounds.49 Other forms of pyogenic myositis which are not due to clostridia include group A streptococcal necrotizing myositis, anaerobic streptococcal gangrene, and synergistic non-clostridial myonecrosis. Group A streptococcal necrotizing myositis Group A streptococcus is a common cause of cellulitis and soft-tissue infections, including abscess formation. Rarely, it manifests as severe myositis, termed group A streptococcal ‘necrotizing myositis’, ‘streptococcal myonecrosis’, or ‘gangrenous myositis’.50 The myositis may occur concurrently with necrotizing fasciitis and/or a toxicshock-like syndrome.51 Most patients developing gas necrotizing myositis had no underlying medical conditions, most were male (2:1 ratio) and younger than 50 years of age.50,51 The disease usually occurs spontaneously, a minority of cases occurring with a history of minor trauma. The clinical presentation consists of severe pain, usually occurring in an extremity (typically the leg), with fever, edema, and sometimes overlying skin findings (Table 4). The disease can be separated into three stages: (1) a prodromal stage with a nonspecific ‘flu-like’ illness including sore throat, a scarletinaform rash, and muscle pain lasting for 3e7 days; (2) a rapid intermediate phase with sudden escalation of the muscle pain over a period of hours; and (3) a late stage with manifestations of bacteremia, toxic shock, multiorgan failure, and/or compartment syndrome accompanying the myositis.
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The diagnosis is suspected on the basis of the clinical presentation. Differentiating myositis from necrotizing fasciitis is difficult, and these entities may occur concurrently. MRI imaging can define the exact location of involvement, but should not delay the need for surgical exploration, which is the gold standard for establishing the diagnosis. Necrotizing fasciitis commonly presents with violaceous bullae on the overlying skin and may help to differentiate these conditions.15 Clostridial myonecrosis is suggested by gas in the tissues. However, neither of these findings is absolute, and the diagnosis rests on findings on surgical exploration and microbiological culture. Laboratory findings are non-specific and usually include leukocytosis and an elevated creatine phosphokinase level; some cases have a normal white blood count and erythrocyte sedimentation rate (ESR) due to the rapid speed of the infection and lack of time for a sufficient immune response to develop.52 Treatment consists of immediate surgical debridement and reassessment of the tissues to evaluate the need for further removal of devitalized tissues. For group A streptococci, the antibiotics of choice include intravenous penicillin G (24 million units daily in divided doses) and clindamycin, 900 mg three times daily; the latter is utilized due to the ‘Eagle effect’ since this antibiotic has good activity against the bacteria in the stationary phase of growth and inhibits toxin production.53 Intravenous immunoglobulin may also be beneficial in cases of toxic shock associated with group A streptococci.54 Research efforts in the area of novel antimicrobial, antitoxin, or immune-regulator medications are needed. Prognosis is guarded, especially in the presence of toxemia, with mortality rates of 30e85%.50,51,55 Improvement in the outcome depends on the rapid recognition of the condition, immediate therapy, and the development of novel treatment strategies.
Anaerobic streptococcal myonecrosis This clinical entity bears similarities to gas gangrene, as it usually occurs in association with a wound, often after trauma, and gas may be present within the tissues. Differentiating findings between the two clinical entities include the absence of early severe pain associated with the wound and the presence of early erythema. Like gas gangrene, the wound commonly has a foul odor (Table 4). The causal agents are typically mixtures of streptococci (group A and anaerobic) and/or S. aureus. Treatment is with surgical debridement and antibiotics. If streptococci alone are present, penicillin is adequate. With the presence of other organisms such as staphylococci additional agents are employed since most staphylococci (>95%) are resistant to penicillin alone.
OTHER FORMS OF BACTERIAL MYONECROSIS Synergistic non-clostridial myonecrosis may occur among patients with vascular insufficiency (e.g. diabetes mellitus, cardiorenal disease, obesity) or among neutropenic patients. This infection involves the skin, subcutaneous tissues, fascia, and muscle; it is usually polymicrobial, with both aerobic and anaerobic pathogens. Similar infections can involve patients with vascular grafts with a variety of organisms, including Bacillus.56 Patients with wounds and exposure to fresh water may develop infection with Aeromonas.57
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MYALGIAS ASSOCIATED WITH EOSINOPHILIA Infectious myositis accompanied by eosinophilia is typically due to a parasitic infection. These disorders characteristically manifest as diffuse myalgias, although specific muscles may be most involved. Trichinosis Trichinosis occurs after the ingestion of insufficiently cooked meat that is contaminated with the parasite Trichinella (most commonly T. spiralis). Generally, the meat involved is pork, although a rising number of cases associated with wild meat e including bear, walrus, seal, cougar, and wild boar e have been reported.58 Patients may develop symptoms 1e2 weeks after ingestion; some infections are subclinical, depending on the size of the inoculum. After ingestion, larvae penetrate the wall of the small intestine of the human and disseminate throughout the body via the bloodstream. The earliest symptoms may include gastrointestinal discomfort, diarrhea, and vomiting. Muscle soreness and weakness may occur as larvae become encapsulated in the muscles; the most common sites include the diaphragm, extraocular, masseter, and tongue muscles, but other sites may be involved. In addition, classic findings include fever, edema of the upper eyelids, subconjunctival hemorrhages, eye pain, and prostration. Complications of trichinosis include both neurological and cardiac involvement due to the deposition of larvae in these areas.14 Laboratory testing shows eosinophilia; an elevated creatine phosphokinase level suggests extensive muscular involvement. The diagnosis is typically established by the classic symptoms of trichinosis along with the food ingestion history. Biopsy of skeletal muscle can show the encysted larvae but is typically not required. Serologic tests, such as the enzyme-linked immunofluorescence assay and the bentonite flocculation assay, are the most common methods for confirming the diagnosis. Of note, these tests usually do not turn positive for 3 or more weeks after infection. The main disease in the differential diagnosis of trichinosis is the eosinophiliaemyalgia syndrome which generally occurs after ingestion of tryptophan. Treatment is with albendazole or mebendazole. These drugs are most beneficial in the early course of the disease since they act at the gastrointestinal stage but have little activity against larvae embedded within the musculature.59 Better antiparasitic drugs with penetration into the muscles are needed to treat myositis. Bed rest and salicylates may be useful. Corticosteroids are reserved for life-threatening disease, including brain or heart involvement; patients with active myositis may also symptomatically improve with steroids in doses of 30e80 mg daily. Disease prevention includes ensuring that meat is adequately cooked (55 C), frozen (25 C for 10 or more days), or irradiated to kill the larvae. Cysticercosis Cysticercosis results from the ingestion of undercooked pork contaminated with Taenia solium eggs; in addition, patients may become infected by ingestion of other food products or water contaminated with eggs. Similarly to trichinosis, the disease disseminates from the upper gastrointestinal tract to the skeletal muscles, central nervous system, heart, and eye. Incubation period is from weeks to years. Muscular symptoms of this infection are uncommon, but myalgias, fever, and eosinophilia may occur. The most
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significant presentation of this disease is the neurological manifestations resulting from the deposition of the organism, including seizures, headaches, or psychiatric disturbances. The diagnosis of muscular involvement is most commonly made when radiological films show calcified cysts (‘puffed rice’ appearance) in the muscles. Occasionally, palpation of the musculature may reveal ‘oval swellings’ between the fibers. Rarely, pseudohypertrophy of the muscles (especially the calves and thighs) can occur with widely disseminated disease.60 Serologic tests are available to confirm the diagnosis. Treatment is praziquantel for intestinal disease. For central nervous system disease, praziquantel or albendazole may be utilized, but care must be taken due to the risk of increasing edema due to cyst death; often, corticosteroids are employed. Infectious disease and neurosurgical consultations should be obtained in these cases. Other parasitic infections Acute schistosomiasis (Katayama syndrome) may manifest as fevers, myalgias, and eosinophilia, as well as abdominal pain, headaches, and diarrhea. This syndrome occurs 2e8 weeks after exposure to the cercariae, which penetrate the skin after exposure to contaminated fresh water in endemic areas, including Africa, the Middle East, Southeast Asia, South America, and Central America. Myalgias may also occur during the acute phase of Chaga’s disease (Trypanosoma cruzi), along with periophthalmic edema (Romana’s sign), fever, headaches, and adenopathy after the bite of a triatomine bug in South or Central America. Toxocariasis, the cause of visceral larva migrans, may rarely present with muscle pain in association with eosinophilia.
Practice points infectious myositis may be caused by viral, bacterial, fungal, or parasitic pathogens pyogenic myositis is classified as clostridial myonecrosis (gas gangrene), group A streptococcus necrotizing myositis, or non-clostridial myositis such as anaerobic streptococcal myonecrosis pyomyositis is an intramuscular infection involving one or more of the skeletal muscle groups and is the result of transient bacteremia not spread from a contiguous site the most common organism associated with pyomyositis is Staphylococcus aureus treatment of pyomyositis consists of drainage, frequently using CT guidance, and intravenous antibiotics psoas abscess usually develops in association with a gastrointestinal disorder or an adjacent vertebral osteomyelitis gas gangrene is a rapidly progressive infection of the skeletal muscle(s) with necrosis and often gas formation the cause of gas gangrene is usually Clostridium perfringens associated with contaminated wounds due to trauma or surgical sites; Clostridium septicum may be implicated in association with a gastrointestinal malignancy
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treatment of gas gangrene and group A streptococcal myositis consists of rapid surgical exploration and debridement, as well as intravenous penicillin G and clindamycin hyperbaric oxygen therapy can be considered in cases of gas gangrene, but there is no clear consensus on its benefit group A streptococcus necrotizing myositis presents with severe pain, usually occurring in the extremity, fever, edema, and sometimes a toxic-shock-like syndrome non-clostridial myonecrosis includes anaerobic streptococcal myonecrosis, synergistic non-clostridial myonecrosis, myositis associated with vascular grafts, and myositis associated with freshwater exposure (Aeromonas) parasitic infections may manifest as myositis with eosinophilia trichinosis develops after ingestion of contaminated pork or wild meat classic findings of trichinosis include fever, edema of the upper eyelids, subconjunctival hemorrhages, and muscle discomfort cysticercosis involvement of the musculature is most commonly recognized on radiologic films showing calcified cysts (‘puffed rice’ appearance)
Research agenda novel diagnostic tests to determine the etiology of myositis, including molecular tools e polymerase chain reaction (PCR), DNA analysis e are needed given the high mortality rates of gas gangrene and group A streptococcal myonecrosis, improved therapies for these conditions, including novel pharmaceutical medications, anti-toxins, and/or immune regulators controlled studies are needed to determine the efficacy of hyperbaric oxygen in cases of gas gangrene treatments which are more effective in treating Trichinella in the muscle compartments and cysticercosis would be beneficial
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