Myositis and Myonecrosis

OVERVIEW: What every practitioner needs to know about myositis

Are you sure your patient has myositis? What should you expect to find?

Infectious myositis is uncommon, and may be due to a wide variety of pathogens, ranging from viruses to invasive microorganisms, such as bacteria, mycobacteria, fungi, and even parasites. In some cases, particularly viral infections, myositis accompanies systemic viral infection and is managed supportively. In the case of invasive bacterial and fungal infections, myositis can be a progressive and life-threatening illness requiring early diagnosis and aggressive management. Most cases of bacterial myositis are due to Staphylococcus aureus and recognized as pyomyositis. However, additional distinct rapidly necrotizing myositis syndromes, such as streptococcal myositis and clostridial myonecrosis, may be recognized by their dramatic clinical presentations, which promote early diagnosis and therapy. Since localized or generalized pain is a prominent and often nonspecific feature of infectious myositis, early diagnosis can be challenging.

Pyomyositis

• Pyomyositis evolves through three clinical stages.

• Symptoms of pyomyositis

  Invasive stage: subacute development of pain, fever, and minimal tenderness at site of infection

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  Suppurative stage: follows 10 to 21 days later, with increased local pain, fever, and tenderness

  Sepsis stage: spread of infection systemically, with systemic symptoms and signs of sepsis

• Signs of pyomyositis

  Invasive stage: variable fever, localized swelling and induration (± erythema), and minimal tenderness

  Suppurative stage: progressive fever, localized muscle tenderness, swelling, with or without fluctuance, and successful aspiration of purulent fluid if attemptedSepsis stage: marked local findings of erythema, fluctuance, exquisite tenderness, and signs of sepsis (i.e., hypotension, shock, etc.)

How did the patient develop pyomyositis?

• In most cases, initially asymptomatic transient bacteremia presumably leads to localized muscle infection. Primary dermatitis or superficial skin infection may increase the risk of transient bacteremia, and prior blunt trauma or vigorous exercise predisposes some individuals to develop myositis at the site of damaged muscle tissue.

• Pyomyositis occurs most commonly in tropical climates, where it accounted for 1 to 4% of hospital admissions several decades ago. In temperate climates, pyomyositis remains very uncommon; about 15 cases are recorded annually in the United States, although it is likely significantly underreported, and has an incidence of 0.5 cases per 100,000 population annually in Australia. It can develop in individuals of all ages, including children and the elderly.

Which individuals are of greater risk of developing pyomyositis?

• Roughly 40% of individuals have no underlying systemic risk factors, but a wide variety of underlying illnesses and/or high risk behaviors (particularly intravenous drug abuse) appear to increase the risk of developing pyomyositis. These include common disorders, such as diabetes mellitus and alcoholic liver disease, and classic disorders of immunosuppression, including human immunodeficiency virus (HIV) infection. Immunosuppressive medications, including corticosteroid therapy are also important risk factors. A variety of less common conditions (hematologic malignancies [i.e., leukemia, lymphoma, multiple myeloma]; other hematologic disorders [i.e., myelodysplasia, sickle cell disease, Felty syndrome, cyclic neutropenia]; rheumatologic disorders, especially rheumatoid arthritis and systemic lupus erythematosus; and postpartum and postoperative states) confer an increased risk of pyomyositis.

• In almost all cases, these underlying processes are clinically prominent by history and routine clinical evaluation at the time myositis develops.

Beware: there are other diseases that can mimic pyomyositis:

• The subacute nature of pyomyositis and paucity of initial findings makes prompt diagnosis challenging.

• In the absence of fever, muscle strain, contusion, and even muscle infarction or rupture may be suspected.

• An enlarging soft tissue mass may be mistaken for a solid tumor, such as a sarcoma.

• When fever accompanies focal pain, possible osteomyelitis or septic arthritis is often considered.

• Rupture of an intramuscular abscess with overlying skin erythema mimics cellulitis.

• Pelvic muscle involvement, including iliopsoas infection, may mimic appendicitis or diverticulitis, and pyriformis involvement may be mistaken for an epidural abscess.

• Occasionally, nonclostridial myositis (e.g., anerobic streptococcal myonecrosis) can resemble pyomyositis, although it usually has a more accelerated tempo of illness.

Group A streptococcal necrotizing myositis

In addition to the slowly progressive pyomyositis syndrome more typically associated with S. aureus, group A streptococcal infection may also cause an extreme rapidly progressive illness evolving more than 24 to 48 hours frequently accompanied by features of streptococcal toxic shock syndrome.

• In contrast to staphylococcal pyomyositis, which often develops in truncal or pelvic musculature, group A streptococcal necrotizing myositis most commonly arises in an extremity.

• Severe and rapidly progressive pain, with marked local swelling accompanied by fever and progressive systemic toxicity, often with features of toxic shock syndrome, are clues to its early diagnosis. As with pyomyositis, a compartment syndrome further threatening muscle viability may develop. Prior streptococcal pharyngitis is uncommon.

• Roughly one-half of all cases of invasive group A streptococcal disease occur in previously healthy individuals. Invasive disease results from the integrated expression of proteases and other virulence factors, coupled with a lack of prior immunity and protective antibody expression in infected individuals (i.e., both pathogen and host factors contribute to the development of this life-threatening infection).

• The dramatic and fulminant presentation of group A streptococcal necrotizing myositis has few clinical mimics. Clostridial myonecrosis, bacterial myositis (due to group A streptococci, S. aureus, or less commonly other bacterial pathogens) with evolution of a compartment syndrome or staphylococcal toxic shock syndrome and group A streptococcal necrotizing fasciitis may all resemble group A streptococcal necrotizing myositis. Skin necrosis and tense bullae are more common with streptococcal necrotizing fasciitis, although both fasciitis and necrotizing myositis develop in concert in some patients.

Clostridial myonecrosis ("gas gangrene")

Clostridial myonecrosis develops following local contamination of injured muscle by clostridia (typically Clostridium perfringens) following penetrating trauma or surgery or as the result of hematogenous seeding in the absence of trauma, primarily by C. septicum. This is usually associated with occult compromise of the colonic mucosal integrity by a previously unrecognized adenocarcinoma or as a complication of neutropenic colitis.

• Clostridia perfringens is part of the normal colonic flora and may naturally contaminate skin surfaces, especially of the perineum and lower extremities. Thus, any local trauma can predispose injured muscle to secondary clostridial invasion.

• Although dramatic injuries, such as penetrating war wounds or severe civilian injuries, especially with open fractures, may precede the development of clostridial myonecrosis, less prominent prior processes, including intra-abdominal surgery, septic abortion, and parenteral injections (even subcutaneous injections), have been reported, and even chronic arterial insufficiency without additional trauma has been reported as a risk factor for clostridial myonecrosis.

  Devitalized tissue and contaminated foreign bodies are major risk factors for the development of gas gangrene; prompt debridement of wounds and delaying wound closure have played major roles in reducing the incidence of these infections.

• Spontaneous nontraumatic disease due primarily to hematogenous seeding by C. septicum does not require significant prior local tissue injury. Occult adenocarcinoma is the major risk factor for the development of this condition, but other bowel lesions, including diverticulitis, bowel infarction, and necrotizing enterocolitis, may trigger this process. Compromise of the colonic mucosa in the setting of neutropenia, seen in leukemic patients receiving cytotoxic chemotherapy, and diabetes are additional risk factors.

• Clostridial myonecrosis should be suspected by its rapid clinical evolution, with progression of severe pain over 6 to 48 hours disproportionate to clinical findings, particularly when risk factors of recent trauma or surgery are present. Local tenderness and swelling are the initial findings, with the expression of a thin malodorous serosanguinous fluid from open wounds. Crepitus in the affected tissue can often be appreciated, and bullae containing similar thin serosanguinous fluid arising from tensely edematous discolored tissue may precede the development of cutaneous necrosis. Acute illness with clinical toxicity, pallor, diaphoresis, followed rapidly by hypotension and tachycardia culminating in shock and renal failure, are present. Interestingly, low grade fever (or even hypothermia) is the rule. The course of illness is rapidly progressive, with visible skin changes advancing and evolving hour by hour in the emergency ward or intensive care unit (ICU).

• Beware: there are other diseases that can mimic clostridial myonecrosis:

  Several distinct soft tissue and muscle infections associated with gas formation may mimic clostridial myonecrosis (clostridial and nonclostridial anerobic [crepitant] cellulitis, nonclostridial crepitant myositis or cellulitis).

  These processes all require surgical exploration and debridement in addition to appropriate antibiotic therapy. Gas production in clostridial anerobic cellulitis typically exceeds that seen with myonecrosis, and the tempo of illness with anerobic cellulitis is typically somewhat slower and associated with less toxicity than in cases of clostridial myonecrosis.

• Since clostridial myonecrosis is the most acutely tissue- and life-threatening gas-producing infection, all patients presenting with crepitant soft tissue infections should be approached aggressively with emergent exploration and intensive support. Broad spectrum antibiotic therapy is appropriate until initial Gram stain and culture data define the etiologic agent or agents and enable more targeted antibiotic therapy.

Other forms of crepitant myositis

• Anerobic streptococcal myonecrosis

  This mixed infection of gram-positive pathogens mimics clostridial myonecrosis in many ways, although its tempo is somewhat slower. A few days following penetrating trauma, patients present with swelling, erythema, seropurulent wound drainage, and progressive pain at the site of injury. There is gas present in the muscles and fascial planes. Gram stain of the drainage fluid and operative specimens shows an inflammatory reaction with polymorphonuclear leukocytes, and evidence of a mixed infection, including streptococci. Wound culture usually recovers both anerobic streptococci (e.g., peptostreptococci) and group A streptococci or S. aureus.

• Synergistic nonclostridial anerobic myonecrosis

  A mixture of anerobic and facultative organisms can cause rapidly invasive soft tissue infection in diabetic individuals and in neutropenic patients. The infection typically begins following minor superficial injury but progressively spreads to deeper structures, including subcutaneous tissue, fascia, and muscle. This is a rapidly progressing infection requiring emergency exploration and debridement and initial empiric broad-spectrum antibiotic therapy.

• Aeromonas hydrophila myonecrosis

  Individuals who sustain penetrating injuries in freshwater settings (e.g., after boating or swimming accidents) or associated with fish or other water-based wildlife may develop a fulminant myonecrosis syndrome, often with gas production and pain, swelling, bullae formation, and marked systemic toxicity that resembles clostridial myonecrosis. The history of freshwater exposure is key for early diagnosis. As with clostridial myonecrosis, emergent surgical debridement and antibiotic therapy is crucial. Aeromonas hydrophila is present in wound drainage and surgical excised tissue and is frequently present in blood cultures obtained on presentation.

• Infected vascular grafts

  Devitalized tissue due to arterial insufficiency/graft thrombosis is the focus of this infection. It occurs in patients with failed vascular grafts, especially in diabetic patients. Unlike the rapidly progressive crepitant myositis syndromes, these infections remain largely localized to the area of vascular insufficiency. The responsible pathogens typically include a mixture of facultative gram-negative rods, such as Proteus species, anerobic streptococci, and anerobic gram-negative rods, such as Bacteroides species.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

• Routine clinical laboratory screening studies, including peripheral white blood cell (WBC) with differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and blood cultures, should be obtained in all patients. Assessment of liver and kidney function tests are important to screen for underlying metabolic disorders, as well as to guide appropriate antibiotic therapy. If pustules, infected traumatic lesions, bullae, or other concerning skin lesions are present, these should be unroofed and sent for routine culture in otherwise normal individuals, and for broader culture, including fungal cultures in compromised hosts and HIV-infected individuals. If a fluctuant soft tissue collection is appreciated or documented by preliminary imaging, this can be aspirated for Gram stain and culture, which should include primary anaerobic culture.

• Patients with truncal or pelvic pain should have urinalysis and urine culture performed as well. Leukocytosis is generally present in almost all forms of bacterial myositis. Evolving leukopenia may be present with delayed or fulminant presentations, particularly in the presence of toxic and/or septic shock.

• A low hematocrit is commonly present in clostridial myonecrosis due to toxin-mediated hemolysis.

• Muscle enzymes (e.g., CPK) are variably elevated and, in fact, often normal in bacterial pyomyositis, but are commonly quite markedly elevated in patients with streptococcal necrotizing myositis.

Results that confirm the diagnosis

• Gram staining of fluid or excised necrotic tissue provides presumptive identification of causative pathogens, and culture of abscess fluid confirms the diagnosis of pyomyositis and the various forms of necrotizing muscle infection and guides specific antibiotic therapy. Patients often undergo definitive drainage of established muscle abscesses after receiving initial (preprocedural) empiric antibiotic therapy, thus, cultures may be unrevealing. In these cases, pretreatment cultures of blood and/or infected skin sites may help to identify the causative pathogen.

What imaging studies will be helpful in making or excluding the diagnosis?

• Imaging plays an essential role in the assessment of patients with focal soft tissue pain and fever to establish the presumptive diagnosis of myositis and guide urgent surgical exploration.

  Plain films may reveal focal soft tissue swelling, the presence of soft tissue gas at the painful site, and possible relevant associated skeletal abnormalities, such as osteomyelitis or a primary bone tumor. $

  Ultrasonography is readily available and can demonstrate focal muscle enlargement in early stage disease, and complex hypoechoic areas in the suppurative stage of disease, reflecting abscess formation. It is also valuable for the prompt assessment of patients with possible gas-forming infections in the emergency ward. $

  Magnetic resonance imaging (MRI) is the most informative single imaging modality, because it identifies focal muscle edema and localized abscess formation with great precision, particularly with gadolinium administration. In patients with rapidly progressive disease, surgical exploration should not be delayed to obtain an MRI study. Gadolinium administration is contraindicated in the setting of renal insufficiency, a complication frequently present in patients with rapidly progressive necrotizing muscle infection. $$$$

  Computed tomography (CT) scanning is generally readily available and rapidly performed. It can demonstrate muscle edema, focal low density (necrotic) muscle abnormalities suggestive of evolving infection, as well as well-established fluid collections often accompanied by ring enhancement. CT scans readily detect the presence of gas in the tissues in patients with clostridial myonecrosis, and contrast-enhanced studies demonstrate the extent of muscle infarction. As with MRI, surgical exploration should not be delayed while awaiting urgent CT imaging, and contrast administration is contraindicated in the setting of renal insufficiency. $$$

• ($ = 60–125, $$ 125–500, $$$ 500–1,000, $$$$ >1000)

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has pyomyositis or necrotizing muscle infection, what therapies should you initiate immediately?

• General Surgery or Orthopedic Surgery and Infectious Diseases should be consulted.

• In addition to the initiation of appropriate antibiotic therapy, urgent drainage of established abscesses and surgical debridement of necrotizing disease in patients with bacterial myositis is critical. In the case of pyomyositis, the selection of open surgical drainage, typically by orthopedic or general surgeons, or percutaneous drainage via ultrasound or CT guidance by interventional radiologists depends on the abscess location, size, complexity, and institutional expertise. Patients with streptococcal necrotizing myonecrosis, clostridial myonecrosis, or other necrotizing crepitant infections should have emergency open exploration to achieve aggressive debridement of necrotic muscle until viable tissue is found.

• Empiric antibiotic therapy for pyomyositis must target the preponderant pathogen S. aureus and should include vancomycin. Additional broad-spectrum coverage against gram-negative pathogens and anerobes should include a beta-lactam/beta lactamase inhibitor combination, such as piperacillin-tazobactam, or a carbapenem agent, such as imipenem, as part of the initial empiric coverage, especially in immunocompromised hosts. Formal Infectious Disease consultation should be obtained when possible to optimize empiric antibiotic selection, refining therapy as the microbiological data becomes available.

• In patients with suspected streptococcal or clostridial myonecrosis, an inhibitor of protein synthesis, such as clindamycin should be added to initial broad spectrum therapy to reduce the production of bacterial exotoxins. Since penicillin is the agent of choice in these fulminant infections, the combination of penicillin, clindamycin, together with empiric coverage for possible mixed infection with a fluoroquinolone, such as ciprofloxacin, or an advanced cephalosporin (e.g., cefepime) is appropriate.

• Appropriate ICU supportive care is necessary in patients with streptococcal or clostridial infection, as well as patients with toxic shock syndrome due to S. aureus pyomyositis, since they require hemodynamic and ventilatory support and blood product replacement therapy.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

Empiric therapy for pyomyositis should target gram-positive pathogens, including S. aureus (both methicillin-sensitive and methicillin-resistant isolates), as well as potential gram-negative pathogens, particularly in compromised hosts. Vancomycin together with a broad-spectrum beta lactam/beta-lactamase inhibitor (e.g., piperacillin-tazobactam) or a carbapenem, such as imipenem, is appropriate initial empiric coverage pending Gram stain and culture of abscess material. In the rare setting in which presumed staphyloccal pyomyositis is complicated by features of toxic shock syndrome, clindamycin should be added, as well as an inhibitor of toxin production.

Streptococcal necrotizing myonecrosis and clostridial myonecrosis, and the related necrotizing soft tissue syndromes outlined above, are presumptively confirmed at the time of surgical debridement or Gram stain and culture of bulla fluid. The initial broad spectrum antibiotic regimens listed above may be initiated at presentation, with inclusion of clindamycin, until preliminary etiologic confirmation has been achieved. Myonecrosis due to group A streptococci or clostridia should be treated with high dose penicillin and clindamycin parenterally once confirmed.

For treatment of specific pathogens, see Table I.