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  1. 1. Lyme Disease Quinnipiac University Physician Assistant Program Lyme Disease Definition •multiorgan rheumatologic disease characterized by inflammation of the connective tissue within the skin, central nervous system, heart, and joints Epidemiology –any age –risk factors: genetic - symptoms worse in those with HLA-DR2 –infection - Borrelia burgdorferi –environment - endemic areas, June/July Pathogenesis •Borrelia burgdorferi is a spirochete which is transmitted in endemic regions to man from ticks of the genus Ixodes - first identified in Lyme, Conn. in 1975 by rheumatologist Dr. Allen Steele of Yale •Dr. Willy Burgdorfer was the first to isolate the spirochete •cattle, dogs, cats, mice can all act as hosts Adult Ixodes scapularis (the smaller of the 2 ticks, also called a deer tick), adult Dermacentor variabilis (dog tick), next to a common match. I scapularis is the vector of Lyme disease, babesiosis, and human granulocyte ehrlichiosis. D variabilis is the vector for Rocky Mountain spotted fever. Clinical Features Constitutional symptoms –headache –lymphadenoapthy –hepatomegaly/hepatosplenomegaly –migratory musculoskeletal pain –chills –testicular swelling –meningismus –dizziness •Stage 1 (Localized Infection) –1. Skin Manifestations (75%) Erythema Chronicum Migrans (ECM)
  2. 2. –initially an erythematous macule or papule at site of tick bite –3 to 32 days later expands into a bull’s eye lesion –red annular lesion with central clearing –indurated red center that may become vesicular or necrotic –often reaches a diameter of 16 cm (3-68 cm) –located anywhere but mostly on the thigh, groin, or axillae Secondary Lesions –malar rash, conjunctivitis, and small evanescent red blotches and circles –develop several days after ECM in up to 50% of patients –smaller in size & lack the indurated centers –not associated with the tick bite –skin manifestations resolve within 3-4 weeks –regardless of treatment, skin manifestations may recur Stage 2 (Disseminated Infection) –rheumatological manifestations (80%) –joint manifestations occur within a week to 2 years after initial illness migratory arthralgias –appear early in course of disease Arthritis –begins months after onset of illness –typically involves large joints (knees) but also small joints –lasts for weeks to months and usually recurs for several years –in 10% becomes chronic neurological (CNS) manifestations (10%) –occur within 4 weeks of initial illness and resolve over 3 months but can recur and may become chronic major (Triad) –1. cranial neuropathy (Bell’s palsy) –2. meningitis –3. peripheral radiculoneuropathy Minor –cerebellar ataxia –demyelinating encephalopathy
  3. 3. –Guillian-Barre –seizures cardiovascular manifestations (8%) •occur within 5 weeks of initial illness and last from 3 days to 6 weeks and rarely recur 1. major –AV block (1st, 2nd [Wenkebach], & 3rd degrees) –cardiomegaly –left ventricular dysfunction –myopericarditis Stage 3 (Persistent Infection) –occurs rarely in children –may last for years rheumatological manifestations –progressive arthritis leading to permanent disability neurological manifestations –depression, intellectual impairment, demyelinating disease Investigations Serum •elevated ESR (50%), IgM (33%), AST (19%) Urine •proteinuria, microscopic hematuria CSF –mononuclear pleocytosis –normal glucose –modest elevation in protein Synovial Fluid –WBC - 500-100,000 –predominance of PMN leukocytes –elevated protein level –slight decrease in C3, C4, and total hemolytic compliment Serologic Tests •ELISA Management
  4. 4. Stage 1 –po amoxicillin or erythromycin (young) or tetracycline (older) for 10-30 days –symptoms resolve rapidly with good rate of success –can prevent the later complications Stage 2 –IV ceftriaxone for 14 days –can cross the blood brain barrier –IV tetracycline or chloramphenicol for those with a penicillin or cephalosporin allergy ] Stage 3 –IV penicillin or ceftriaxone Rocky Mountain Spotted Fever •RMSF prevalent rickettsial disease in the United States and is growing •first recognized in parts of Idaho and Montana it has since been reported throughout the United States •two thirds of RMSF patients are under 15 years of age •there is still a regular mortality rate of 5- 7% •deaths in children with RMSF are attributable to –atypical initial symptoms –late onset of rash –failure to consider the diagnosis •Rickettsia rickettsii –consists of small coccobacillary microorganisms –similar to that of gram negative bacteria •onset of disease usually occurs 2- 8 days after an infected tick bite –Wood tick, Dog tick, Lone Star tick •has a marked seasonal character with most cases occur during the period of greatest tick activity from April to September Clinical Features •focal areas of thrombosis and leakage of RBC's into the surrounding tissues appear to account for clinical manifestations –fever, rash –headache –mental confusion
  5. 5. –terminal heart failure and shock •vascular lesions found most readily in the skin, gonads, and adrenal glands •rash of RMSF is an important pathognomonic feature –appearing by the second or third day in most patients –the initial lesions are small erythematous macules which blanch on pressure –lesions rapidly become maculopapular and petechial confluently hemorrhagic –the rash appears first peripherally on the wrists and ankles with spreading to the trunk –especially diagnostic is its regular occurrence on the palms and soles •fever rises rapidly and may be as high as 105o •Neurologic symptoms include –seizure disorders –cortical blindness –central deafness –ataxia –spastic paralysis •congestive heart failure and arrhythmias are common •profound muscle tenderness is a common feature Investigations •profound hyponatremia is common and is related to extracellular shift of fluid, urine loss, and exchange of sodium for potassium at the cellular level •thrombocytopenia •R. rickettsii may be identified by immunofluorescent techniques in skin biopsies Treatment •Doxycycline •aggressive supportive care •mortality still hovers between 5- 7% –death primarily occurs in patients in whom the diagnosis is delayed until the second week of illness •patients with G-6-PD deficiency represent a disproportionate number of case fatalities Ehrlichiosis
  6. 6. •Ehrlichia organisms are one of several kinds of intracellular bacteria grouped with rickettsiae •nonmotile, gram negative intracellular bacteria •predominantly animal pathogens •six species of Ehrlichia were thought to produce disease in animals and human beings •E. Chaffeensis has been identified as the cause of human ehrlichiosis •human ehrlichiosis was first reported in the United States in March 1986 •cases have been primarily recognized along the Atlantic coast and in South Central areas •approximately 75% of human patients with Ehrlichiosis have a history of tick bite •most of the remaining patients report having been in a tick-infested area •median age of patients with ehrlichiosis is 42 y/o –compared with 31 years for patients with RMSF –patients can be as young as 2 years old •human ehrlichiosis has a wide clinical spectrum –inapparent infection –mild viral-like illness –severe life threatening disease Clinical Features •incubation period range from 1 to 21 days •clinical manifestations –nonspecific and are similar to those observed in patients with RMSF •onset of illness is abrupt or subacute with fever that is usually high and often remains elevated despite treatment with antipyretic •patients may also have chills, headache, myalgia, anorexia, nausea or vomiting •gastrointestinal symptoms are slightly more common in children •60% of children have a rash compared to 40% in adults •rashes reported in children were erythematous, macular, papular, vesicular, petechial, scarlatiniform or vasculitic •arthralgia, conjunctival injection, meningitis, pulmonary manifestations and pharyngitis have also been reported in children Investigations •most common laboratory findings include leukopenia, lymphopenia, and thrombocytopenia •may become more marked during the course of the illness
  7. 7. •anemia is less frequent, usually noted in around a third of the patients •liver enzymes are increased early in illness both in adults and children •renal abnormalities: –elevated blood urea nitrogen and –serum creatinine concentration, –proteinuria, and –hematuria may be present –renal failure has not been a feature of ehrlichiosis in children. •hyponatremia is not a common finding in human ehrlichiosis •children usually have an excellent prognosis with resolution of abnormalities within 1 to 2 weeks •differential diagnosis most often include RMSF –may also include leptospirosis, Kawasaki, tularemia, lyme disease, meningococcemia, leukemia, and collagen vascular disease Treatment •Doxycycline appears to be the drug of choice Hand, Foot, and Mouth Disease Defintion •viral infection of the skin and oral mucosa characterized by vesicular eruptions restricted to the hands and feet and in the mouth Epidemiology •incidence: common •age of onset: any but usually in young children •risk factors: summer and fall in small epidemics Pathophysiology •first described in 1957 •etiological agents –major - coxsackievirus A16, A5, and A10 –minor - enterovirus 71 •route of transmission –? direct person to person transmission •incubation period –4-6 days
  8. 8. •clinical expression rate –young children (100%) –school-aged children (38%) –adults (11%) Clinical Features Cutaneous Manifestations •hands and feet –hands more commonly involved than the feet –dorsal surfaces more commonly involved than the palmar surfaces (often interdigital) –initially maculopapular lesions which form into grey-white vesicles on a normal or erythematous base –vesicles are from 3-7 mm in size and painless –a maculopapular rash commonly appears on the buttock but rarely goes on to form vesicles •intraoral lesions –tongue and buccal mucosa most frequently involved with the palate, gums, and lips less frequently involved –vesicles may go on to ulcerate –vesicles are from 4-8 mm in size •systemic manifestations –low-grade fever –adenopathy Investigations Serum •CBC - leukocytosis Management •Supportive –tylenol 15 mg/kg po q4h for fever Prognosis –self-limited and vesicles disappear after 1 week