Autopsy- Case Reports:
Unknown female, 40, Maryland
Johns Hopkins Death- Autopsy Report40 year old woman misdiagnosed with MS. Had positive Lyme serology, symptoms; medications were stopped, she died.
Case No: 7.
Autopsy No.: #26488
Age (decades): 40
Sex: F
Decade of Autopsy: 1990
Key Number: 26972
diagnosis multiple sclerosis age ;.
progressive deterioration neurologic status requiring total care admission ;.
intravenous adrenocorticotropic hormone ;.
adjustment medications ;.
phenobarbital ;.
positive LYME serology ;.
admission meridian nursing center hills ;.
paraplegia ;.
postural tremor ;.
recurrent ;.
coli urinary tract infection ;.
aspiration thin liquids ;.
increased difficulty swallowing ;.
decreased oral motor control ;.
five pound weight loss past six months ;.
declining mental status ;.
patient family decision gastrostomy tube placement secondary patient wishes
against artificial life support ;.
initiation comfort care only orders ;.
discontinuation food fluids ;.
elevated temperatures degrees ;.
shallow respirations ;.
apneic spells ;.
decreased responsiveness ;.
death hours ;.
extensive multiple periventricular demyelinated plaques bilateral cerebral
hemispheres cerebellum basal ganglia brainstem high levels cord ;.
brain weight ;.
moderate hydrocephalus vacuo ;.
purulent material ;.
bacterial overgrowth bronchi bilateral lungs consistent ;.
aspiration ;.
focal hemorrhage small foci acute bronchopneumonia apical posterior basilar
bilateral lungs ;.
combined weight ;.
squamous metaplasia urinary bladder ;.
cause death part ;.
multiple sclerosis ;.
Unknown female, 70, Maryland
Johns Hopkins Death- Autopsy ReportCase No: 26.
Autopsy No.: #46758
Age (decades): 70
Sex: F
Decade of Autopsy: 1990
Key Number: 810547
appendectomy ;.
hysterectomy ;.
bladder repair ;.
osteoarthritis ;.
family history cerebrovascular accident cancer ;.
tick bite ;.
onset nausea ataxia right facial weakness ;.
admission local ;.
diagnosis LYME disease nervous system ;.
elevated serum cerebrospinal fluid igm igg titers borrelia burgdorferi ;.
intravenous ceftriaxone ;.
transfer progression cranial nerve deficits ;.
lyme disease ;.
secondary bell palsy cerebellar involvement ;.
right lid lag ;.
heberdeen nodules ;.
elevated serum cholesterol ;.
aspiration pneumonia ;.
pleocytosis ;.
mononuclear per lumbar puncture ;.
area increased signal ;.
weighting noted right cerebellar peduncle ;.
enhanced ;.
gadolinium ;.
white matter lesions corona radiata per magnetic resonance imaging ;.
multiple temperature spikes ;.
enterobacter species per sputum culture ;.
broad spectrum antibiotics ;.
right vocal cord paralysis per nasopharyngeal endoscopy ;.
acute respiratory arrest ;.
intubation ;.
extubation required one hour ;.
chest radiograph consistent ;.
new bilateral aspiration pneumonia ;.
admission stereotatic biopsy pontine lesion ;.
left gaze paresis anisocoria right cornea decreased sensation bell palsy uvula deviated right ataxia upper extremities ;.
consistent ;.
right pontine lesion ;.
blot negative lymph disease ;.
negative rheumatoid factor ;.
serum rapid plasma reagin positive ;.
broad spectrum antibiotics ;.
pulmonary infiltrates per chest radiograph ;.
anemia ;.
small left pleural effusion sonography ;.
atelectasis pleural effusion negative lymphadenopathy negative definite masses per computerized tomography ;.
extensive necrosis ;.
lymphocytes atypical poorly preserved suggestive negative diagnostic small cell malignant neoplasm per nervous system sterotactic needle aspiration ;.
necrotic tissue cannot determine specimen represents necrotic brain abscess tumor per pons needle biopsy ;.
steroid therapy ;.
tracheostomy ;.
mechanical ventilation ;.
hypotensive episode responsive fluid resuscitation ;. feeding tube ;.
heme positive loose stools ;.
conjunctivitis treated ;.
topical gentamicin ;.
right gaze palsy ;.
leukocytosis ;.
percutaneous endoscopic gastrostomy tube placement ;.
elevated cerebrospinal fluid glucose per lumbar puncture ;.
extremely atypical ;.
background mononuclear per cerebrospinal fluid analysis ;.
left subclavian venous line ;.
hypotensive episode responsive fluid resuscitation ;.
increasing bilateral atelectasis versus infiltrates per chest radiography ;.
antibiotic therapy ;.
enterobacter per sputum culture ;.
stable ring enhancing lesions posterior pons decreasing cortical edema exam less distortion fourth ventricle per magnetic resonance imaging study ;.
diarrhea ;.
positive assay clostridium difficile toxin ;.
weaning ventilator ;.
pulmonary toilet ;.
supraventricular tachycardia per electrocardiogram responsive verapamil ;.
recurrent atelectasis left lower lobe per chest radiograph ;.
continuous positive airway pressure maintain airway ;.
empiric flagyl ;.
right subclavian line ;.
maltophilia per sputum culture enterobacter ;.
enterococcus ;.
per urine culture ;.
cardiopulmonary arrest ;.
successful cardiopulmonary resuscitation ;.
coma score ;.
neurological exam consistent ;.
brain death ;.
heparin ;.
lidocaine pressor agents ;.
atrial tachycardia ;.
intermittent atrial flutter fibrillation per electrocardiogram ;.
increased arterial alveolar oxygen gradient ;.
burst suppression pattern consistent ;.
severe anoxic brain injury per electroencephalogram ;.
negative resuscitate status ;.
death ;.
well differentiated primary cns lymphoma ;.
associated hemorrhage necrosis right inferior cerebellar peduncle brain ;.
severe ischemic ;.
anoxic ;.
encephalopathy cerebral cortex cerebellum brain ;.
lacunar infarcts midbrain putamen brain ;.
adenoma right kidney ;.
acute chronic pancreatitis pancreas ;.
chronic passive congestion intrahepatic cholestasis steatosis liver ;.
organizing pneumonia right left lower lobes lung ;.
focal active pneumonitis lungs ;.
scattered cytomegalovirus intranuclear inclusions ;.
organized thromboemboli lung ;.
leiomyomas stomach esophagus ;.
congestion edema lungs ;.
weight gms ;.
calcified granulomas ;.
greatest diameter ;.
lower lobe left lung ;.
mild atherosclerosis left anterior descending right coronary arteries heart ;.
cardiomegaly ;.
left ventricular hypertrophy heart ;.
fatty infiltration right ventricle heart ;.
atherosclerotic plaque ;.
stenosis superior mesenteric artery ;.
moderate complicated atherosclerosis aorta ;.
mild atherosclerosis pulmonary artery ;.
degenerative joint disease vertebra ;.
hemorrhagic urethritis cystitis urinary bladder ;.
hematomas rib fractures anterior chest wall thorax ;.
cardiopulmonary resuscitation ;.
ulcer gastroesophageal junction ;.
cytomegalovirus inclusions underlying endothelium ;.
diverticulosis colon ;.
tracheostomy tube trachea ;.
heberdeen nodes nodes radial deviation distal
interphalangeal phalanges hands ;.
mild pedal edema ;.
surgical absence uterus ovaries ;.
hysterectomy ;.
Unknown male, 30, Maryland
Johns Hopkins Death- Autopsy ReportCase No: 2.
Autopsy No.: #22718
Age (decades): 30
Sex: M
Decade of Autopsy: 1990
Key Number: 698753
spinal disc surgery years ago ;.
isoniazid treatment positive purified protein
derivative ;.
erythematous rash right eyelid ;.
swelling tenderness left wrist ;.
erythematous papules bilaterally ;.
bilateral shoulder myalgia ;.
prednisone treatment ;.
improvement musculoskeletal complaints rash ;.
progressive dyspnea ;.
outpatient chest computerized axial tomography
revealing bilateral interstitial lung infiltrates ;.
scaly red rash extensor surfaces elbows knees ;.
painful oral ;.
fifteen pound weight loss ;.
presentation emergency room progressive dyspnea ;.
pulmonary function tests revealing mixed obstructive restrictive lung disease ;.
normocytic anemia ;.
elevated liver function tests ;.
electromyography nerve conduction studies revealing myopathy ;.
irritative consistent ;.
dermatomyositis ;.
muscle biopsy ;.
revealing negative specific pathologic changes ;.
fatty liver per computerized axial tomography ;.
positive immunosorbent assay LYME disease ;.
negative rheumatologic workup ;.
ana rheumatoid factor ;.
spiral computerized axial tomography chest revealing mass right lower lobe ;.
vocal cord leukoplakia ;.
skin biopsy ;.
direct immunofluorescence showing granular igm igg along basement membrane consistent ;.
dermatomyositis ;.
temperature elevation ;.
bronchoscopy ;.
lavage positive pneumocystis carinii cytology ;.
revealing pulmonary macrophages lymphocytes occasional histiocytic aggregates suggestive granulomatous inflammation ;.
respiratory decompensation followed respiratory distress hypoxemia ;.
transfer medical intensive care unit ;.
progressive insufficiency ;.
intubation ;.
adult respiratory distress syndrome ;.
hypoxemia requiring ;.
treatment ;.
broad spectrum antibiotics including bactrim
pneumocystis ;.
thrombocytopenia hemolysis ;.
pneumomediastinum pneumopericardium subcutaneous emphysema ;.
oxide trial ;.
right upper quadrant ultrasound progressive insufficiency revealing fatty liver distended gallbladder ;.
treatment ;.
intravenous immunoglobulin ;.
hypotension ;.
leukopenia ;.
bone marrow biopsy ;.
showing hypocellular marrow ;.
virtual absence granulocytes dyserythropoiesis hemophagocytosis ;.
withdrawal supportive measures ;.
death ;.
extensive infarction necrosis hyaline membrane disease ;.
occasional atypical pneumocytes lungs ;.
organizing thrombi vascular changes ;.
proliferation lungs ;.
moderate interstitial fibrosis lungs ;.
contraction band necrosis ;.
nuclear degeneration heart ;.
hypocellular bone marrow ;.
depletion granulocytes megakaryocytes dyserythropoiesis hemophagocytosis ;.
congestion white pulp depletion hemophagocytosis spleen ;.
hemorrhagic microinfarct cerebellum brain ;.
multiple microinfarcts medulla frontal cortex occipital cortex brain ;.
moderate myopathic changes skeletal muscle ;.
distension ;.
biliary sludge gallbladder ;.
steatosis cholestasis liver ;.
superficial erosions ;.
stomach ;.
focal fat necrosis pancreas ;.
spermatogenic arrest ;.
submucosal hemorrhage anterior tongue ;.
focal atherosclerotic stenosis left anterior descending artery heart ;.
serosanguineous effusions right ;.
left ;.
pleural cavities ;.
serosanguineous effusion ;.
pericardium ;.
numerous crusting skin erosions ;.
measuring ;.
corpus ;.
cause death ;.
part ;.
pulmonary infarction necrosis ;.
dermatomyositis ;.
Unknown male child, 11, Maryland
Johns Hopkins Death- Case ReportCase Report: The patient is an eleven-year-old African American male who was in his previous state of good health until approximately one-month before presentation when he developed a swelling in his left groin that was progressively increasing in size. He was seen approximately three weeks later by his primary physician who diagnosed inguinal lymphadenitis and treated with Keflex. He was also immunized with the varicella vaccine. A PPD was placed which was negative.
One day before presentation, he developed a headache, sore throat, and aching back and legs while at school. He was treated symptomatically at the school clinic and his headache resolved. The following day, he was noted to have a mild tremor in both hands and some dragging of his left foot. That evening he developed a generalized tonic-clonic seizure and was promptly brought to the ER.
In the ER, he was actively seizing and apneic. He was intubated and loaded with phosphenytoin. He received a dose of ceftriaxone and a non-contrast head CT was normal. He was transferred to the PICU. Other than a mild leukocytosis, his initial labs were unremarkable and included a negative toxicology screen. His seizures remained difficult to control requiring multiple anti-seizure agents including propofol drip. He had intermittent fevers and was treated with acyclovir and cefepine beginning on the second hospital day. Bacterial and viral cultures from the blood and CSF were negative. Serology for HIV and EBV was negative and PCR testing for HSV was also negative.
The patient never regained consciousness and he continued to decline with lactic acidosis and cardiac failure. He died on the fifth hospital day. Further history revealed that the patient had been exposed to a new kitten approximately 1.5 months before presentation. Serologic testing of his serum for Bartonella henselae and quintana (performed at the CDC) are shown in Table 1. Serologic tests and PCR tests of the CSF for Bartonella henselae were negative.
Table 1.
Serologic testing for Bartonella henselae and B. quintana using IFAB. henselae B. quintana
IgG (H&L) 512 2048
IgG (gamma) 128 512
IgM 128 128Bartonella henselae/Cat-scratch disease encephalopathy
Organism: The causative organism of cat-scratch disease encephalopathy is Bartonella henselae, a small, gram-negative and extremely fastidious rod. Bartonella species are oxidase negative and aerobic. Recovery of Bartonella spp. has been accomplished using chocolate agar or other media without antimicrobials incubated for at least 21 days in 5% CO2 at 35 to 37°C. B. bacilliformis, geographically confined to the South American Andes, is an erythrocyte-invasive bacterium associated with severe febrile illness and profound anemia.
Its vector is the sand fly Lutzomyia verrucarum. B. quintana was first recognized as the cause of "trench fever" seen in battlefield troops of World War I and is transmitted by the body louse. Transmission of B. henselae has been firmly linked with felines and evidence suggests that the cat flea is a potential vector among animals. The incidence of Bartonella infections in immunocompromised patients is not known. In immunocompetent patients, approximately 10 instances of cat scratch disease (CSD) per 100,000 persons occur annually in the United States with approximately 60% of cases occurring in persons under 20 years of age.2
Clinical Manifestations: Symptoms associated with bacteremia in B. henselae in immunocompromised patients are characterized by insidious development of fatigue, malaise, body aches, weight loss, progressively worsening fevers and headache. Both B. henselae and B. quintana are associated with bacillary angiomatosis, vascular proliferative lesions seen almost exclusively in immunocompromised patients. Bartonella infection in immunocompromised patients can also cause bacillary peliosis hepatitis (formation of venous lakes in the liver), endocarditis, and bacteremia.
Instances of Bartonella bacteremia and endocarditis have been reported in immunocompetent patients but the incidence is thought to be very low. More commonly, CSD is seen in immunocompetent patients infected by B. henselae. The primary cutaneous lesion of CSD occurs 3 to 10 days after a cat scratch or bite. This wound gradually resolves. Regional adenopathy, the hallmark finding in CSD, occurs approximately 10 days after the injury. One third of patients will also present with fever lasting 1 to 2 weeks. Approximately 2% to 3% of patients will develop Parinaud’s oculoglandular syndrome characterized by regional lymphadenitis and unilateral conjunctivitis. Neurologic involvement is seen in approximately 2% of cases.3 CSD encephalopathy has recently been reported as a cause of status epilepticus in children.
Diagnosis: As described above, diagnosis of Bartonella spp. by culture is slow and difficult. Antibodies to B. henselae have been demonstrated in between 88% and 95% of patients with CSD using both an indirect immunofluorescence assay and enzyme immunoassay. Using IFA, higher relative titers of B. quintana are frequently seen in CSD cases but are thought to represent cross-reactivity. PCR assays using 16S rDNA primers specific to Bartonella spp. have also been successful in diagnosis.3
Treatment:
Immunocompromised patients: Erythromycin 500mg q6h or Doxycycline 100mg q12h for 12 weeks.Immunocompetent patients: No specific antimicrobial therapy recommended.
Fatal Cases of Rocky Mountain Spotted Fever in Family Clusters --- Three States, 2003
CDC-MMWR May 21, 2004 / 53(19);407-410Rocky Mountain spotted fever (RMSF), a tickborne infection caused by Rickettsia rickettsii and characterized by a rash, has a case-fatality rate as high as 30% in certain untreated patients (1). Even with treatment, hospitalization rates of 72% and case-fatality rates of 4% have been reported (1--3). This report summarizes the clinical course of three fatal cases of RMSF in children and related illness in family members during the summer of 2003. These cases underscore the importance of 1) prompt diagnosis and appropriate antimicrobial therapy in patients with RMSF to prevent deaths and 2) consideration of RMSF as a diagnosis in family members and contacts who have febrile illness and share environmental exposures with the patient.
Case Reports:
Unknown female child, 7, OklahomaOklahoma. In late May, a female child aged 7 years was taken to an emergency department (ED) with 2 days of fever (102.7º F [39.3º C]), malaise, abdominal pain, nausea, and vomiting. Viral gastroenteritis was diagnosed, and the patient was released. Four days later, the patient reported to a second ED with persistent fever, anorexia, irritability, photophobia, cough, diffuse myalgias, nausea, and vomiting. Physical examination showed hepatosplenomegaly and an erythematous papular rash with scattered petechiae on the trunk, arms, legs, palms, and soles. Laboratory results included an elevated white blood cell (WBC) count of 11.4 x 109 cells/L (normal range: 3.0--9.1 x 109 cells/L), thrombocytopenia (19 x 109 platelets/L [normal range: 150--350 x 109 platelets/L]), elevated aspartate aminotransferase (AST) of 279 U/L (normal: <42 U/L), and elevated alanine aminotransferase (ALT) of 77 U/L (normal: <48 U/L). In the ED, the patient was treated with intravenous (IV) doxycycline for suspected RMSF and transferred to a pediatric intensive care unit at a tertiary care medical center, where she had declining mental status, metabolic acidosis, and respiratory failure; the patient died 6 days after initially seeking treatment. IgG antibodies reactive with R. rickettsii at a reciprocal titer of 128 were demonstrated by using an indirect immunofluorescence antibody (IFA) assay in a serum specimen collected 2 days before death. Spotted fever group rickettsiae (SFGR) were detected by immunohistochemical (IHC) staining at CDC in autopsy specimens from the brain, skin, heart, lung, spleen, and kidney.
On June 1, the child's sister, aged 3 years, had fever, headache, myalgias, and vomiting; on the following day, she had an erythematous maculopapular rash on the trunk, extremities, palms, and soles. RMSF was diagnosed, and the child was treated with doxycycline; she recovered. Seroconversion of IgG antibodies reactive with R. rickettsii was demonstrated in acute and convalescent phase serum specimens obtained during illness and 5 months later. Both children played frequently in grassy areas near their home. No history of tick bite was reported, although ticks were frequently observed on the family's pet dogs and often were manually removed by members of the household.
Unknown male child, 2, Kentucky
Kentucky. In early August, a male child aged 2 years was taken to a pediatrician after 1 day of fever (101.0º F [38.3º C]) with a papular rash on his legs, arms, trunk, and back. An unspecified viral syndrome was diagnosed, and the child was treated with nonsteroidal anti-inflammatory drugs. During the next 2 days, the child continued to have fevers, spiking to 102.0º F--103.0º F (38.9º C--39.4º C), and variable rash. The child was examined in an ED and discharged with a diagnosis of viral infection. Four days after initial treatment, the child was again evaluated by a pediatrician because of lethargy and refusal to walk. Laboratory tests showed thrombocytopenia (42 x 109 platelets/L), a WBC count of 3.3 x 109 cells/L, anemia (hemoglobin 10.4 g/dL [normal range: 13.8--17.2 g/dL]), and hyponatremia (134 mmol sodium/L [normal range: 135--145 mmol sodium/L]). The next day, the child was admitted and treated with IV ceftriaxone and methylprednisolone. Two days later, the child was transferred to a tertiary care hospital. Physical examination at admission revealed a fine petechial rash on the groin, trunk, ankles, and palms. The patient was treated with IV vancomycin, cefotaxime, and doxycycline. His condition continued to deteriorate; 8 days after initial treatment, he died from multiple system failure. A serum specimen collected 2 days earlier tested positive by enzyme immunoassay for IgM antibodies reactive with R. rickettsii at 9.4 index value units (index values >2.0 were considered reactive by the testing laboratory). SFGR were detected by IHC stain in autopsy specimens of the brain, skin, heart, lung, spleen, kidney, lung, and adrenal gland.
The child's mother, aged 40 years, was hospitalized 2 days before her son's death with 2 days of diplopia, dizziness, headache, and fever. Oral doxycycline and IV ceftriaxone were administered; she was discharged after 5 days. Seroconversion of IgG antibodies reactive with R. rickettsii was demonstrated in acute and convalescent phase serum specimens obtained during illness and 2 weeks later. The family lived near a lake with woods. The mother did not recall any recent tick bites, travel, or participation in outdoor activities, by herself or her son prior to illness onset.
Unknown male child, 14 months, ArizonaArizona. In mid-August, a male child aged 14 months was taken to a community health clinic after 1 day of fever (103.7º F [39.8º C]), with a maculopapular rash, including the palms and soles, and thick white exudates on the tongue. Chest radiographic evaluation showed a possible right lower lobe infiltrate. The child was treated with intramuscular cefotaxime, acetominophen, and antifungal medication for presumptive thrush. The next day, the child visited the clinic with nausea, vomiting, anorexia, and dehydration. The patient was transferred to a referral hospital for treatment of pneumonia, roseola infantum, and thrush; on admission, the patient had a temperature of 105.7º F (41º C). After 3 days, he was transferred to a tertiary care hospital with a diagnosis of sepsis and disseminated intravascular coagulopathy. The patient was treated with IV ceftazidime and vancomycin. Laboratory findings included an elevated WBC count (16.2 x 109 cells/L), thrombocytopenia (46 x 109 platelets/L), and elevated levels of AST (291 U/L) and ALT (99 U/L). Six days after initial treatment, the child died of pulmonary hemorrhage; an autopsy was not performed. A serum specimen obtained 5 days before the child's death tested negative by IFA for IgM and IgG antibodies reactive with R. rickettsii; however, R. rickettsii DNA was amplified from serum by polymerase chain reaction (PCR) assay. A serum specimen obtained from a brother, aged 5 years, showed IgM and IgG antibodies reactive to R. rickettsii, indicating recent exposure. The children lived in a rural environment with low shrubs and grasses and frequently interacted with free-roaming dogs with ticks; however, neither child had a history of recent tick bite.
Reported by: C Levy, MS, J Burnside, MS, T Tso, Arizona Dept of Health Svcs. S Englender, MD, M Auslander, DVM, S Billings, DVM, Div of Epidemiology and Health Planning, Kentucky Dept for Public Health. K Bradley, DVM, J Bos, MPH, L Burnsed, MPH, Div Communicable Diseases, Oklahoma Dept of Health. J Brown, MD, D Mahoney, MD, K Chamberlain, M Porter, C Duncan, B Johnson, R Ethelbah, K Robinson, M Wessel, S Savoia, MD, C Garcia, J Dickson, D Kvamme, D Yost, MD, M Traeger, MD, Indian Health Svc. J Krebs, MS, C Paddock, MD, W Shieh, MD, J Guarner, MD, S Zaki, MD, D Swerdlow, MD, J McQuiston, DVM, WL Nicholson, PhD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; L Demma, PhD, EIS Officer, CDC.
Consequences of Delayed Diagnosis of Rocky Mountain Spotted Fever in Children --- West Virginia, Michigan, Tennessee, and Oklahoma, May--July 2000
Patients with Rocky Mountain spotted fever (RMSF), a tickborne infection caused by Rickettsia rickettsii, respond quickly to tetracycline-class antibiotics (e.g., doxycycline) when therapy is started within the first few days of illness; however, untreated RMSF may result in severe illness and death. Persons aged <10 years have the highest age-specific incidence of RMSF (1,2). This report summarizes the clinical course and outcome of RMSF in four children from four regions of the United States and underscores the need for clinicians throughout the United States to consider RMSF in children with rash and fever, particularly those with a history of tick bite or who present during April--September when approximately 90% of RMSF cases occur (1,2).
West Virginia
On May 12, a child aged 15 months presented to a physician with a 2-day history of maculopapular rash and fever. A tick had been removed from the patient's scalp 1 week before onset of symptoms. The patient was thought to have a viral illness. On May 16, the patient returned to the physician with continued fever and irritability; an allergy to a sulfa-containing antimicrobial prescribed on the previous visit was suspected, and treatment was switched to an oral penicillin-class antibiotic. On May 17, the patient was seen twice at a local emergency department (ED) and, by the second visit, exhibited lethargy, seizures, a generalized petechial rash, hyponatremia (131 mmol of sodium/L) (normal range: 135--145 mmol/L), and thrombocytopenia (8 x 109 platelets/L) (normal range: 150--350 x 109/L). The patient was transported to a tertiary medical center with a differential diagnosis of bacterial sepsis, meningitis, or a rickettsial disease and immediately was started on intravenous doxycycline. Shortly after admission, the patient required intubation for respiratory distress and anticonvulsant therapy for seizures. On May 19, the patient died. Paired serum samples demonstrated a four-fold increase (from 80 to 320) in reciprocal IgM antibody titers reactive with R. rickettsii when tested using an indirect immunofluorescence assay (IFA). When stained by using an immunohistochemical (IHC) technique, tissue samples obtained at autopsy demonstrated spotted fever group rickettsiae.
Michigan
On June 1, a child aged 3 years presented to a physician with a 4-day history of rash and a temperature of 101.3 F (38.5 C). On clinical examination, the patient had a fine red-purple rash on the cheeks, trunk, upper extremities, and palms, thrombocytopenia (102 x 109/L), and a normal white blood cell (WBC) count (5.8 cells x 109/L). The patient's mother reported that she recently had found a tick on the patient's scalp. The patient was diagnosed with a viral exanthem. On June 2, the patient was still febrile but the rash had faded, and the patient was given an oral cephalosporin-class antibiotic. On June 5, the patient developed vomiting, decreased appetite, persistent crying, and disorientation. The patient's mother reported that she had removed a second tick that day. Clinical examination revealed generalized petechiae, hepatosplenomegaly, dry mucous membranes, and pallor. Laboratory findings included thrombocytopenia (38 x 109/L), an elevated WBC count (19 x 109/L), hyponatremia (124 mmol/L), elevated aspartate aminotransferase (AST 7.20 µkat/L) (normal range: 0.17--0.67 µkat/L), and alanine aminotrans ferase (ALT 1.63 µkat/L) (normal range: 0.17--0.92 µkat/L). The patient was admitted to a hospital, and within several hours the patient became cyanotic, developed seizures, and died. Using an IHC stain, tissue samples obtained at autopsy revealed spotted fever group rickettsiae. Using a polymerase chain reaction assay, a whole blood sample was positive for DNA of R. rickettsii.
Tennessee
On June 15, a child aged 11 years presented to an ED with a 1-day history of severe headache and a temperature of 102.4 F (39.1 C). On clinical examination, an injected tympanic membrane was found, and the patient received an oral penicillin for otitis media and released. No history of tick bite was reported. On June 16, the patient developed a diffuse maculopapular rash, and on June 20, the patient was hospitalized because of persistent fever, headache, and vomiting; a viral exanthem or an allergic reaction to the antibiotic was suspected. Laboratory findings included elevated AST (0.96 µkat/L) and ALT (1.52 µkat/L). On June 24, the patient was treated intravenously with a cephalosporin and sent home; however, the patient continued to have fever and headache. On June 30, IFA results from a serum sample obtained June 21 revealed positive IgG and IgM antibody titers (64 and 64, respectively) reactive with R. rickettsii. The patient received oral doxycycline and the symptoms resolved over the next 7 days. On July 6, IFA results of a serum specimen demonstrated an eight-fold increase in the IgG antibody titer to 512, confirming the diagnosis of RMSF.
Oklahoma
On July 7, a child aged 6 years presented to a physician with a 1-day history of a temperature of 102.2 F (39.0 C), headache, myalgia, diarrhea, and a macular rash on the arms, legs, palms, and soles. On July 1, a tick had been removed from the back of the patient's neck. On July 10, the patient was diagnosed with a viral illness. When the symptoms worsened, the patient was given an oral cephalosporin. On July 11, the patient was hospitalized with dehydration, irritability, confusion, and thrombocytopenia (26 x 109/L). On July 12, the patient was transferred to a tertiary care medical center with disseminated intravascular coagulation. Laboratory results included an elevated WBC count (20 x 109/L) and AST (3.65 µkat/L), and thrombocytopenia (9 x 109/L). On July 13, therapy with intravenous doxycycline for possible RMSF was initiated. The patient subsequently developed gangrene, requiring limb amputation and removal of the upper stomach and distal esophagus. On August 19, the patient died. Using an enzyme immunoassay, a serum sample collected on July 12 tested positive for IgG antibodies reactive with R. rickettsii. Serum obtained on August 3 and tested using an IFA demonstrated a high positive IgG antibody titer of 1024 reactive with R. rickettsii.
Reported by: L Minnich, MS, JE McJunkin, MD, Charleston Area Medical Center, Charleston; D Bixler, MD, C Slemp, MD, L Haddy, MA, State Epidemiologist, West Virginia Dept of Health and Human Resources. F Busse, MD, M Harrison, MD, Lakeland Medical Center, Lakeland; MG Stobierski, DVM, ML Boulton, MD, State Epidemiologist, Michigan Dept of Community Health. T Jones, MD, W Moore, MD, State Epidemiologist, Tennessee Dept of Public Health. P Barton, MD, St. Francis Hospital, Tulsa; K Bradley, DVM, M Crutcher, MD, State Epidemiologist, Oklahoma State Dept of Health. State Br, Div of Applied Public Health Training, Epidemiology Program Office; Infectious Disease Pathology Activity, and Viral and Rickettsial Zoonoses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; and EIS officers, CDC.
Editorial Note:
Despite its name, RMSF has been reported throughout the continental United States (except in Maine and Vermont) (1,2). During 1990--1998, approximately 4800 RMSF cases were reported to CDC. Approximately 20% of the cases and 15% of reported deaths were in persons aged <10 years. Because of RMSF's rapid course, half the RMSF deaths in this age group occurred within 9 days of illness onset, leaving no more than several days to establish the diagnosis and initiate specific antibiotic therapy. Before the discovery of effective antirickettsial drugs, 13% of children with RMSF died (3). Despite the availability of treatment and advances in supportive medical care, the case-fatality ratio is 2%--3% for patients aged <10 years with RMSF (Figure 1).
In its early stages, RMSF may resemble other infectious and noninfectious conditions and can be difficult to diagnose even for physicians familiar with the disease (4,5). Because only 3%--18% of patients present with rash, fever, and a history of tick exposure on their first visit (4--6), physicians should consider RMSF in infants and children even when one feature is lacking. The absence of tick exposure should not dissuade the clinician from suspecting RMSF. Laboratory abnormalities such as thrombocytopenia and hyponatremia should also raise the possibility of RMSF (5).
Delayed diagnosis and late initiation of specific antirickettsial therapy (e.g., on or after day 5 of the illness) is associated with substantially greater risk for a fatal outcome (1,4,5). Treatment never should be delayed pending a laboratory diagnosis. Most broad-spectrum antibiotics, including penicillins, cephalosporins, and sulfa-containing antimicrobials, are ineffective treatments for RMSF. In almost all clinical situations, including disease in children aged <8 years, the antibiotic of choice is doxycycline (7). However, this drug is used infrequently as initial therapy even for children who present with signs and symptoms of a rickettsial illness (6). The use of tetracyclines in young children has been discouraged because of the potential for tooth discoloration and should be reserved for patients in whom a rickettsial illness is strongly suspected; however, tetracycline staining of teeth is dose related and available data suggest that one course of doxycycline for presumed RMSF does not cause clinically significant staining of permanent teeth (8).
The most effective ways to reduce the risk for RMSF in children are for supervising adults to 1) limit the child's exposure to ticks, especially during April--September; 2) thoroughly inspect the head, body, and clothes for ticks after time spent in wooded or grassy areas, especially along the edges of trails, roads, or yards; and 3) immediately remove attached ticks by grasping the tick with tweezers or forceps close to the skin and pulling gently with steady pressure. More information about RMSF is available on the World-Wide Web, http://www.cdc.gov/ncidod/dvrd/rmsf.
http://www.cdc.gov/mmwR/preview/mmwrhtml/mm4939a2.htm
“Pride is concerned with who is right. Humility is concerned with what is right.”– Ezre Taft Benson
© 2006 The National Lyme Disease Memorial Park Project
