ITP - Rocky Mountain spotted fever - idiopathic thrombocytopenia

From: JWissmille (jwissmille_at_aol.com)
Date: 09/27/04 

Date: 27 Sep 2004 22:46:53 GMT

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 ľkat/L) (normal range: 0.17--0.67 ľkat/L),
and alanine aminotrans ferase (ALT 1.63 ľkat/L) (normal range:
0.17--0.92 ľkat/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 ľkat/L) and ALT (1.52 ľkat/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 ľkat/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 theillness) 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.

References

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