The wildfire fighter with arthritis and fatigue
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The wildfire fighter with arthritis and fatigue. ID Case Conference Wednesday July 25 th , 2007 David P. Fitzgerald, MD. HPI.

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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


The wildfire fighter with arthritis and fatigue

HPI

  • 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.


The wildfire fighter with arthritis and fatigue

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.


The wildfire fighter with arthritis and fatigue

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.


The wildfire fighter with arthritis and fatigue

HPI

  • June - Referred to ID clinic

  • She had been off of antibiotics since 5/30.

  • Reported feeling rather well.

    • 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.


The wildfire fighter with arthritis and fatigue

HPI

  • 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


The wildfire fighter with arthritis and fatigue

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

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.


The wildfire fighter with arthritis and fatigue

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

Allergies/Medications


Physical exam

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.

Physical exam


The wildfire fighter with arthritis and fatigue

November 2006

WBC 4.0

Nml 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

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)

Data


The wildfire fighter with arthritis and fatigue

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

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

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

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 191

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

Clinical

  • 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

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

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

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

  • By the time the rash develops the child feels well and is no longer contagious (detectable IgM – clears viremia)


Arthritis

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


Arthritis1

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

Diagnosis

  • 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)

  • Previous infection

    • Document for pregnancy with positive IgG

  • 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

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

Manifestations of B19 InfectionCommon

  • 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

Manifestations of B19 InfectionLess Common

  • Skin

    • Vesiculopustular eruption

    • Henoch-Schonlein purpura

    • Thrombotic thrombocytopenic purpura

    • “Gloves and socks” syndrome

  • Hematological

    • Anemia

    • Thrombocytopenia

    • Leukopenia

    • Benign acute lymphadenopathy

    • Hemophagocytic syndrome


Manifestations of b19 infection less common1

Manifestations of B19 InfectionLess 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

Viral causes of arthritis

  • 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


Parvovirus

Parvovirus

  • Discovered in 1974

  • Only member of family Parvoviridae known to be pathogenic in humans

  • Causes

  • Erythema infectiosum – fifth diseases


Search pubmed

Search PubMed

  • Human Parvovirus B19

    • Case Reports

    • Reviews

    • Differential Diagnosis

    • Drug Therapy


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