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Infectious Myositis: Infectious myositis is an uncommon acute, or chronic infection of skeletal muscle. Most often seen in young adults. The most common infectious agent is the bacterium, Staphylococcus aureus (77-90% of Myositis cases)(prevalent in tropical countries). Viruses, other bacteria (including Mycobacteria), fungi, and parasites can cause myositis. It consists of a primary abscess, edema, and hypoechoic inflammatory Mass. a Viral etiologies typically cause diffuse 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. Bacterial pyomyositis: Pyomyositis consists of a primary muscle abscess and is prevalent in tropical countries. It is associated mainly with immunocompromised patients, and intravenous drug abusers who traumatically contaminate their muscles with foreign material. The clinical presentation is often nonspecific with muscle aches and a deep induration. This may at first suggest an intramuscular neoplasm. The causative agent is Staphylococcus aureus in over 90% of cases. Streptococcus Myonecrosis: -Streptococcal myositis is a rare, often fatal, acute infection of the muscle, caused by an invasive group A beta-haemolytic Streptococcus. -It is characterized by muscle necrosis without abscess formation, and, in contrast to necrotizing fasciitis, does not primarily affect the subcutaneous tissue or skin. -It is a predisposing factor or septic shock. -Management: - high-dose intravenous antibiotics. - intensive fluid and nutritional support. Streptococcal toxic shock syndrome. Clostridium Myonecrosis: (Gas gangrene): Clostridial Myonecrosis is a bacterial infection that produces gas (tissues) in gangrene (necrotic damage of tissue specifically muscles). It is a deadly form of gangrene usually caused by Clostridium perfringens bacteria. This bacterium causes Myonecrosis via specific exotoxins . -In general, different clostridium species are opportunistic and enter the body via significant skin breakage. The exotoxin is commonly found in C. perfringens type A strain and is known as alpha toxin. a The alpha toxin is a phospholipase requiring zinc for activation. First, The C-terminal domain binds calcium and allows the toxin to bind to the phospholipid head-groups on the cell surface. The N-terminal domain has phospholipase activity. This property allows hydrolysis of phospholipids such as phosphatidyl choline to diacylglycerol. N The end result includes activation of arachidonic acid pathway and production of thromboxane A2 (vasoconstrictor), production of IL-8, plateletactivating factor, and several intercellular adhesion molecules. These actions combine to cause edema due to increased vascular permeability. Clinical presentation of Clostridium perfringens infection : a Tetanus ( lockjaw disease): It is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin (Alight chain, B-heavy chain), a neurotoxin produced by the Clostridium tetani. Infection occurs through wound contamination and often involves a cut or deep puncture wound. N - As the infection progresses, muscle spasms develop in the jaw and elsewhere in the body. - Mortality rates reported vary from 48% to 73%. - In recent years, approximately 11% of reported tetanus cases have been fatal. Pathophysiology: - Tetanus begins when endospores of Clostridium tetani enter damaged tissue. - The spores transform into rod-shaped bacteria and produce the neurotoxin tetanospasmin. - This toxin is inactive inside the bacteria. N When the toxin is released , it will be activated by proteases. Active tetanospasmin enters at neuromuscular junctions of motor neurons, B-chain (heavy) binds to neuronal membrane sphingolipid. The light- A chain carried by axonal transport of peripheral nerve terminals to cell bodies in the spinal cord and brain stem where it binds to receptors at these sites. a -The A-chain, a zinc endopeptidase, attacks the vesicleassociated membrane protein ( synaptobrevin ) of central nervous system neurons. -The action of the A-chain stops the affected neurons (inhibitory synapses) from releasing the inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine. -Consequence dangerous overactivity in the muscles from the smallest stimulus. Clostridium tetani also produces an oxygen-labile hemolysin called tetanolysin that destroy the muscle protein. Forms of tetanus: Generalized tetanus : It is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. The first sign is lockjaw, and the facial spasms called risus sardonicus ( Sardonic smile), followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. N Other symptoms include elevated temperature, sweating, elevated blood pressure, and cardiac arrhythmias. Other forms: Neonatal , localized and cephalic tetanus. Clinical presentation of Clostridium tetani: Muscle spasms in a patient suffering from tetanus. Painting by Sir Charles Bell, 1809. Facial spasms called Risus SardonicusFirst Symptom of Generalized Tetanus. Neonatal Tetanus. Laboratory diagnosis: Clinical specimens: Pus swab, exudate (thioglycolate media). C. perfringens: Beta surrounded by Alpha hemolysis. Beta hemolytic filamentous C. tetani. Parasitic Myositis: Trypanosoma cruzi : Transmission : when the Winged bug of the genus Triatoma deposits feces on the skin surface and subsequently bites; the human host. Late ( chronic) stage infection: affects the nervous system, digestive system and cardiac muscle. The protozoa will infect Skeletal muscle by its Amastigote stage. Amastigote stage in skeletal muscle. Trichinella spiralis : It is a nematode parasite, occurring in rats, pigs, and humans, and is responsible for the disease trichinosis. Humans typically become infected when they eat improperly cooked pork (Trichinella infected) meat. Female Trichinella worms stay for about six weeks, in small intestine, and in that time can produce up to 1,500 larvae. Larvae will migrate with blood to striated muscles causing myositis. The muscles invaded mainly are: pectoral muscles, tongue, and the gastrocnemius. Cysticercosis: Cysticercosis involves infection of individuals with the larval stage of Taenia solium, the cysticerci, which normally infects pigs. Autoinfection may occur due to fecal-oral transmission. The oncosphere ( hexacantho-embryo) penetrates the intestinal wall and migrates in the circulation to the tissue ( skeletal muscles). Rabies: Virology: The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae. Lyssaviruses have helical symmetry, with a length of about 180 nm and a cross-sectional diameter of about 75 nm. These viruses are enveloped and have a single-stranded RNA genome Electron microscopy Show the helical Enveloped single stranded RNA virus. a Rabies is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals. The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection usually, but not always, is the animal bite. N The infection is initiated by inoculation of virus into skeletal muscles, virus will be replicated in muscle and transferred to peripheral nervous system. The rabies virus travels to the brain by following the peripheral nerves. Rabies kills around 55,000 people a year, mostly in Asia and Africa (2010). a a Osteomyelitis: Osteomyelitis is the infection of the bone or bone marrow. It can be classified on the basis of the causative organism (pyogenic bacteria or mycobacteria), the route, duration and anatomic location of the infection. Pathogenesis: Microorganisms may infect bone through one or more of three basic methods: via the bloodstream, from local areas of infection (as in cellulitis), penetrating trauma, joint replacements or internal fixation of fractures or root-canaled teeth. A Once the bone is infected, leukocytes enter the infected area, and engulf the infectious organisms, release enzymes that are associated with bone lyses. Pus spreads into the bone's blood vessels, impairing their flow, and cause necrotic dead area of the bone called sequestra , form the basis of a chronic infection. Often, the body will try to create new bone around the area of necrosis. The resulting new bone is often called an involucrum . Causes of Osteomyelitis: a Age group: Most common organisms Newborns (younger than 4 mo) S. aureus, Enterobacter species, and group A and B Streptococcus species Children (aged 4 mo to 4 y) S. aureus, group A Streptococcus species, Haemophilus influenzae, and Enterobacter species Adult S. aureus and occasionally Enterobacter or Streptococcus species Vertebral osteomyelitis Staphylococci (50%), and Tuberculosis (50%). Osteomyelitis : clinical picture: a Septic arthritis: Septic arthritis is the invasion of a joint by an infectious agent which produces arthritis. People with artificial joints are more at risk than others. Septic arthritis is considered a medical emergency. If untreated, it may destroy the joint in a period of days. The infection may also spread to other parts of the body. Prevalence, and pathogenesis: The incidence of septic arthritis has been estimated at 2 to 10 cases per 100,000 in the general population, and as high as 30 to 70 cases per 100,000 in patients with rheumatoid arthritis. Pathogenesis: -Routes of Entry: 1- Dissemination of pathogens via the blood. hematogenous 2- From contaminated needle. 3- Dissemination from soft tissue infection, entry via penetrating trauma. a -Primary infection: -The Synovial A cell (APC) engulfs the microbe. - Production of TNF, IL-8, and PLAF. - Chemotaxis, cellular infiltration, and edematous edema. - Toxic free radicals production. - Proteoglycan and collagen destruction, cartilage destruction. - Direct pressure necrosis, more cartilage destruction. - Specific T-cell response, and Polyclonal B cell activation. Secondary: Osteomyelitis. a Bacteria that are commonly found to cause septic arthritis are: 1-Staphylococcus aureus - the most common cause in adults; (40-50% of cases). Others: 10-20%: 2-Streptococci - the second most common cause 3-Haemophilus influenzae - was the most common cause in children but is now uncommon in areas where Haemophilus vaccination is applied. 4-Neisseria gonorrhoea - in young adults 5-Escherichia coli - in the elderly, IV drug users and the seriously ill. Signs and Symptoms of Septic arthritis: Patients with septic arthritis usually present with : 1-Joint pain. 2-Redness over the joint. 3-Joint inflammation and swelling. 4-Synovial fluid accumulation. Synovial fluid analysis: 1- Physical examination: The normal appearance of a sample of synovial fluid is usually: A-Straw colored. B-Clear. C-Moderately Viscous. A Changes in the physical characteristics may provide clues to the disease present such as: A-Less viscous fluid may be seen with inflammation. B-Cloudy synovial fluid may indicate the presence of microbes, white blood cells, or crystals. C-Reddish synovial fluid may indicate the presence of blood. N 2-Chemical examination: A-Glucose: typically lower than blood glucose levels. -Could be significantly decreased with joint inflammation and infection. B-Protein: increased with bacterial infection. C- Lactate dehydrogenase: -increased LD (LDH) level may be seen in rheumatoid arthritis, infectious arthritis. D-Uric acid—increased with gout. N 3-Microscopic examination : Normal synovial fluid has small numbers of white blood cells (WBCs) and red blood cells (RBCs) but no microorganisms or crystals present. Specimens should be concentrated by centrifugation for: A-Total WBCs count: could be elevated. B-Differential count: Neutrophils increased with bacterial infection. Eosinophils elevated in Lyme disease. N C-Gram’s stain: for detection of Gram-positive and negative bacteria. D-AFB (Z.N stain) smear: for Mycobacterium tuberculosis. 4-Culture and sensitivity test: specimens should be cultured on blood and chocolate agar and incubated at aerobic and anaerobic (10%CO2) conditions respectively. Neisseria and Haemophilus species grow only on chocolate agar.