Transcript The wildfire fighter with arthritis and fatigue

The wildfire fighter with
arthritis and fatigue
ID Case Conference
Wednesday July 25th, 2007
David P. Fitzgerald, MD
HPI
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38 yo WF with history of chronic low back pain presenting
in June 2007 with a 9 month history of a constellation of
symptoms including fatigue, arthralgia, headache and
intermittent fever.
October 2006 - She reports an initial illness with fevers,
headache and nausea/vomiting.
 Was seen by her primary physician and noted to have a rash –
which apparently began on her palms and soles and spread over
her trunk and face.
 She had serological testing for Rocky Mountain spotted fever and
Ehrlichia and was treated empirically with doxycycline x10 days.
Had resolution of hers sxs at that time.
 When she discontinued the doxycycline she developed recurrence
of low grade fevers, joint pain and fatigue and was given another
course of doxycycline.
HPI
► December
- Referred to UNC rheum for
continued arthralgias and fatigue
 Noted to not have any active arthritis or
inflammation on physical exam
 RMSF serology (convalescent) done and
consistent with recent infection.
 Rheum panel negative.
► Treated
with another course of doxycycline.
► Also treated with Mobic.
HPI
► April
- patient sought the opinion of a “tick borne
illness” expert in Virginia –
 a member of the International Lyme and Associated
Diseases Society (ILADS)
 Was diagnosed as having RMSF, ehrlichosis and
babesiosis, despite negative RMSF, ehrlichia and
babesiosis serologies, negative babesiosis DNA PCR and
no history of travel to areas endemic for this babesiosis
 Prescribed a prolonged course of mepron, azithromycin
and doxycycline but stopped after 3 weeks due to GI
intolerance and a rash.
HPI
► June - Referred to ID clinic
► She had been off of antibiotics
► Reported feeling rather well.
since 5/30.
 Her only complaints were intermittent low-grade temps,
up to low 99s.
 moderate fatigue.
 mild aching back and neck. Does not notice any active
inflammation in her joints.
 mild headache intermittently.
 Denied night sweats, chills, weight loss.
 She says these symptoms are all progressing slightly
over the last several days.
HPI
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Sick contacts
 She does note sick contacts including her two children who are age
4 and 6.
 She states that both of her children had “otitis media” and fever for
which they were prescribed amoxicillin in the fall.
 Both children broke out into a diffuse rash one to two days after
starting the antibiotic. This was called a drug reaction and the
antibiotics were discontinued. They were switched to new
antibiotics.
 She states that her children did not experience sore throat or
lymphadenopathy.
 Daughter continued for prolonged period with some arthralgias and
back pain and has had an MRI as work up
PMH
► 1.
Chronic low back pain.
► 2. Hypercholesterolemia.
► 3. Status post tonsillectomy and
adenoidectomy in 1975.
► 4. Fracture of left foot in 1993.
► 5. Kidney stone in 2001.
► 6. C-section for 2 of her children in 2000
and 2002.
Social History
► Lives
with her husband and two children.
► They have several outdoor pets including dogs,
cats, horses, and mules.
► She works for the US Fish and Wildlife Service.
 She spends most of her days out doors in the forest.
 Frequent tick bites and other insect bites
► In
her spare time, she rides horses avidly.
► She denies any tobacco or illicit drugs. She very
rarely drinks beer or wine.
FH
► Her
father had CABG
► Her mother is a breast cancer survivor and
also has essential thrombocytosis and
Sjogren's syndrome.
► She has a sister with melanoma.
► Her maternal grandmother has rheumatoid
arthritis
Allergies/Medications
► Allergies
 Pencillin – rash and
hives
 Sulfa – rash and hives
► Medications
 Mobic prn
Physical exam
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T 36.3, pulse of 68, and blood
pressure of 106/66 RR 16 Sat 98%
HEENT: Pupils are equal, round,
reactive to light and
accommodation. Extraocular
movements are intact. Sclerae are
anicteric. Oropharynx is clear
without any lesions or thrush.
NECK: Supple. There is no anterior
cervical, posterior cervical or
supraclavicular lymphadenopathy.
There is no axillary or inguinal
lymphadenopathy noted.
HEART: Regular rate and rhythm.
No murmurs, rubs, or gallops.
LUNGS: Clear to auscultation
bilaterally.
ABDOMEN: Soft, nontender,
nondistended, no
hepatosplenomegaly.
► EXTREMITIES: No clubbing,
cyanosis or edema.
► SKIN: Nails, the patient has on her
left thumb area at the distal portion
of her thumbnail, which appears to
be lifted off of the base and has
some brown discoloration.
► NEUROLOGIC: The patient is alert
and oriented x3 with nonfocal neuro
exam. Cranial nerves II through XII
are grossly intact.
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Data
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November 2006
 WBC 4.0
► Nml
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diff
Hgb 12.7
Plts 218
Basic panel and LFTs wnl
ANA negative
RMSF serologies “negative”
Lyme IgM and IGG negative
RMSF serology ”negative”
Basic panel and LFTS WNL
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December 06
 WBC 5.2 HGB 13.6 Plt 196
 EBV serologies c/w prior
infxn
 CMV IGG and IGM – neg
 RMSF IFA 1:160 (nml<1:20)
 RMSF LA <1:16 (nml <1:16)
 EHRLICHIA IGG 1:64
(nml<1:64)
 Ehrlichia IGM<1:20
(nml<1:20)
Labs
► April
2006
► Ehrlichiosis HGE IgG < 1:64.
► HGE IgM < 1-20.
► RMSF IgG and IgM listed as negative.
► Lyme Western blot IgG negative except for 1
reactive band at the 41 KD.
► Lyme Western Blot IgM all bands negative.
► Babesiosis antibody IgG negative at < 1:16
 IgM negative at <1: 20.
 Babesiosis DNA which was not detected.
Summary
► 38
yo WF wildfire fighter with frequent
insect exposure with 8-9 months of
relapsing fevers, arthralgias, fatigue
following an initial illness with fever, HA,
N/V and rash.
► Serological evidence of old RMSF and
ehrlichia infection
► Sxs resolve somewhat with doxycycline but
then recur
Diagnostic testing
► HIV
seronegative and pooled negative
► Hep A, B and C negative
► Parvovirus B 19 PCR positive on 33.5 (out of
45) cycles
► Parvovirus IgM positive 4.55 (nml < 1.25)
► Parvovirus IgG positive 5.05 (nml<0.9)
Parvovirus B 19
► Erythrovirus
genus within the family Parvoviridae
 Small non-enveloped SS DNA virus
 Humans are only known host
 Replicates in erythroid progenitor cells of bone marrow
and inhibit erythropoesis
► Discovered
in 1975 while screening units of blood
for Hep B (sample 19 in panel B was a false
positive)
► First associated with clinical disease in 1981
Parvovirus B 19
 Respiratory transmission, vertical transmission
or blood transfusions
 Worldwide distribution
 Late winter and early summer
 During outbreaks in schools 25-50% of children
and 20% of susceptible staff infected
 >70% of adults have IgG levels +
Clinical
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Causes a spectrum of clinical manifestations
25% completely asymptomatic
50% with non specific flu-like illness
25% with classic EI or arthralgia
Biphasic pattern
► Incubation
period 4-14 days
► First week after infection have intense viremia with non specific
flu like illness with fever, malaise, myalgia, HA and pruritis
 Hematological abnormalities with reticulocytopenia, decreased
hemoglobin, leukopenia and TCP
► In
the following week develop rash or arthralgia
Course of disease
Virologic, immunologic & clinical course
following B19 infection.
► See Figure 143-3 in:
Mandell, Bennett, & Dolin: Principles and
Practice of Infectious Diseases, 6th ed.
Full text available via the UNC-CH Libraries
Fever/rash of childhood
► First
Disease – Measles
► Second disease – Scarlet fever
► Third disease – Rubella
► Fourth disease – enterovirus (coxsackie and
echo)
► Fifth disease – Erythema Infectiosum
► Sixth disease – HHV6/7 – infantim subitum
or Roseala infantum
Erythema infectiosum
► Slapped
cheek following non specific viral illness
► Constitional sxs coincide with viremia
► 2-5 days later rash develops
 Slapped cheek with erythematous malar eruption
 followed by a reticulated or lacy rash on trunk or
extremities
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the time the rash develops the child feels well
and is no longer contagious (detectable IgM –
clears viremia)
Arthritis
► One
of the viral causes of arthritis
► Can present with acute arthritis or be mistaken for
rheumatoid arthritis if no rash present
► More common in adults and especially women
► Usually symmetric
► Frequently involve small joints of hands, wrists,
knees and feet
► 75% develop rash (but <20% with malar rash)
► Usually resolve in 3 weeks
Arthritis
► May be persistent or recurring
► May be misdiagnosed as RA
► However does not cause joint destruction
► B19 DNA has been found in joint fluid, but
unclear
if it infects synovial cells
► Often will have associated malaise, fever, fatigue,
GI sxs
► Can have asymptomatic periods between flares
► One half of patients with chronic course meet the
ARA criteria for RA
► Absence of nodules or erosions helps differentiate
Diagnosis
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Acute infection
 Serology – IgM – measurable 7-10 days after exposure and for
several months after
► IgG
– fourfold increase in IgG is also diagnostic
 PCR – can be detected for months following infection (especially in
bone marrow and synovial fluid)
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Previous infection
 Document for pregnancy with positive IgG
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Reactivation or chronic infection
 Confirmed by demonstrating the presence of virus over a prolonged
period
 IgM may also be measurable over long periods if pt is
immunocompetent
 Failure to dx in pts with persistent arthritis is common as IgM may
be negative
Treatment
► For
arthritis main treatment is NSAIDS
 Usually resolves
► For
persistent viremia with clinical disease in
immunocompromised patients IVIG is used
Manifestations of B19 Infection
Common
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Asymptomatic infection
Transient aplastic crisis
Erythema infectiosum
Hydrops fetalis
Acute and chronic arthropathy
Chronic or recurrent bone marrow suppression
in immunocompromised hosts
Manifestations of B19 Infection
Less Common
► Skin
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Vesiculopustular eruption
Henoch-Schonlein purpura
Thrombotic thrombocytopenic purpura
“Gloves and socks” syndrome
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Anemia
Thrombocytopenia
Leukopenia
Benign acute lymphadenopathy
Hemophagocytic syndrome
► Hematological
Manifestations of B19 Infection
Less Common
► Vasculitis
 Polyarteritis nodosa
 Wegener’s granulomatosis
► Liver
 Hepatocellular enzyme elevations
 Non-A, non-B, non-C fulminant liver failure
► Nervous
system
 Paresthesias
 Meningitis
 Sensorineural hearing loss
Viral causes of arthritis
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Parvovirus
Hepatitis A, B and C
Rubella and rubella vaccine
Alpha viruses
 Chikungunya, Ross river, Barmah forest, O’nyong-nyong, Karelian
fever, Ockelbo, Pogosta
Mumps
► Enteroviruses
► Adenovirus
► Herpes viruses –VZV, EBV, HSV, CMV
► HIV
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Parvovirus
► Discovered
in 1974
► Only member of family Parvoviridae known
to be pathogenic in humans
► Causes
► Erythema
infectiosum – fifth diseases
Search PubMed
► Human
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Parvovirus B19
Case Reports
Reviews
Differential Diagnosis
Drug Therapy