Infectious Disease Masquerading as Systemic JRA

1
Infectious Disease Masquerading as Systemic JRA

• The Case of the Disappearing Rash
• Jendi Haug, MD
• Department of Pediatrics
• University of Texas Health Science Center at San
  Antonio

2
Abstract

• A case study presents a 7 year old female with a
  3 week history of daily fevers and a rash of
  unknown etiology. Her unusual presentation with
  right hip pain and a rash that recurred and
  disappeared in relation to her spiking fevers
  was most indicative of systemic onset Juvenile
  Rheumatoid Arthritis and skewed initial treatment
  plans. Infectious etiologies were among the
  patients broad differential diagnosis of fever
  of unknown origin (FUO) that were considered
  during her hospital admission. Not until blood
  cultures grew gram negative coccobacilli were
  detailed dietary and family medical histories
  documented, leading to the diagnosis of
  Brucellosis, later culture confirmed. This case
  serves as a reminder that the clinical picture of
  Brucellosis is nonspecific, that the disease has
  not disappeared as a cause of FUO, and that
  diagnosis hinges on documenting the details of
  diet and recent travel.

3
History

• 7 yr/o HF presents to ED with R hip pain s/p
  trauma, persistent rash to face 3 week h/o
  daily spiking fevers to 101F
• Pt visited Mexico 1 month prior to presentation
  and injured R hip after falling approximately 4
  feet from the top of outdoor steps onto her R hip

4
History

• Pt has been limping and c/o pain to the R hip
  since the time of the injury 3 wk prior
• Per MOC, pain had initially improved, but
  recently returned and seems worse
• Also, 3 week h/o loose stools beginning several
  days after returning from Mexico
• 1 wk prior to admission, pt went to her PCP with
  the c/o R hip pain and persistent nonbloody
  diarrhea

5
History

• PCP noted Pt had very significant limp.
• With pts h/o R hip pain and diarrhea, presumed
  Dx of Salmonella, so stool culture performed
  Cefdinir started
• Once on the Cefdinir, pt developed an
  erythematous, maculopapular rash on both cheeks
  that then remained unchanged since its onset.
• Pt completed the 7 day Cefidinir course.

6
History Admission

• PCP sent pt to ED with presumed septic hip
  temps to 103.2 axillary despite 7 days of
  Cefdinir
• Pt admitted.
• ROS on admission Negative - diarrhea in past 3-4
  days, cough/URI sxs, vomiting, anorexia, weight
  loss, rash other than on face, headache, throat
  pain, dysuria/frequency/change in urine color,
  pain or limited ROM of other extremities
• Positive - minimal abd pain, R hip
  pain/limp

7
Admission History

• PMH/PSH Hosp - 6 mo of age for RSV, 2 yo for
• tonsillectomy and bilat PE tubes
• Birth Hx Term, repeat C/S, 7 lbs, no
  complications during pregnancy, delivery or
  postnatally
• Fam Hx Denies autoimmune or rheumatologic d/o.
• Social Hx Lives with POC (only
  Spanish-speaking), 4 sibs, dog, cat, duck,
  rabbit. No smokers. Pt is in 2nd grade and
  makes A-Bs. No recent h/o diarrhea/fevers in
  other family members or contacts.
• Imm UTD
• Dev Normal
• All NKDA
• Meds Ibuprofen prn, s/p 7 day Cefdinir course

8
Admission Physical

• VS 98.3 123 24 117/67 97 RA
• PE wt 39kg (gt97th) ht 133cm (90th ) BMI 22
  (gt97th )
• Gen Pt sitting cross-legged on the bed, happy,
  alert, appropriate, no distress. Body habitus
  obese.
• Skin discrete erythematous macular lesions on
  both cheeks o/w no other rash R hip - large, TTP
  healing bruise laterally surrounding small
  healing abrasion
• HEENT nc/at, EOMI, PERRLA, OP- clear, nl
  dentition TMs- nl but bilat sclerosis, nares-
  no d/c, no rash to nasal bridge
• Neck no LAD, no thyromegaly
• Lungs CTA bilat, no wheeze/crackle/rhonchi
• CV RRR, 2/6 SEM at the LUSB, nl S1 and S2, 2
  pulses bilat, brisk CR
• Abd soft, nt/nd, normoactive bowel sounds, no
  HSM or mass
• Ext no c/c/e, WWP, no limp, FROM all 4
  extremities with both passive and active
  movement, pain with R hip flexion- pt points to
  external bruise as source of pain, no inguinal
  LAD
• Neuro DTRs 2 UE/LE, CN cerebellar intact,
  strength sensation nl

9
Admission Labs

• CRP 3.97
• ESR 37
• Rapid Strep (PCP office) negative
• Stool culture (PCP office) negative

10
Hospital Course

• On night of admission, pt had Tmax to 105. Blood
  cultures ordered to be drawn x 3 with every spike
  in temp. H.O. called for 105 temp spike noted
  pt to have a new diffuse, faint erythematous
  maculopapular, nonpruritic rash on entire body.
  The rash disappeared once pt became afebrile.

11
Hospital Course

• Despite the history, septic joint was not felt to
  be likely based on physical examination findings.
• Pt continued to have daily temperature spikes of
  100.5-105F through 4 days of the hospital
  course, each time diffuse body rash reappearing
  and facial rash worsening.
• Between fevers, the body rash would disappear
  the facial rash would become less prominent.

12
Hospital Course

• Work up
• Infectious disease
• Rheumatologic disease
• Malignancy

13
Hospital Course

• Radiographic Studies R hip sono and Xray- wnl
• Labs
• CBC WBC 14.5 H/H 10.0/29.8 Plts 238
• MCV 77 RDW 13.9 MD 50/7/37/5
• Chem Na 139 K 5.3 Cl 106 HCO3 24 BUN 10
  
• Cr 0.5 Glu 98 Ca 7.7 Phos 3.5 Mg 2.6
• LFTs Tp 5.9 Alb 3.2 TB 0.2 AST/ALT
  29/3 AlkPhos 109
• LDH 432 Uric Acid 2.6 CK 92

14
Hospital Course

• Labs, continued
• UA 1 bacteria o/w wnl Urine Culture no
  growth
• ANA lt11000
• CRP 3.53
• Rheumatoid Factor 15
• Stool Hemoccult negative
• Viral/Bacterial Titers
• Bartonella, EBV, CMV, Parvo not elevated
• Brucella, Toxoplasma Pending

15
Hospital Course

• History and PE findings of Concern
• Rash with fever
• Daily fevers for extended period of time
• H/o prolonged large joint pain
• H/o recent travel to Mexico
• Labs of Concern
• LDH 432
• Rh Factor 15
• H/H 10/29.8

16
Discussion

• Differential Diagnosis - Fever of Unknown Origin
• Infectious Disease (Rule out first.)
• Localized infection Septic joint, osteomyelitis,
  transient synovitis, UTI, intra-abdominal
  abscess, endocarditis, URI
• Cat scratch disease
• Tularemia
• Salmonellosis
• Rickettsial
• Leptospirosis
• Mononucleosis
• Mycobacterial infection
• Toxoplasmosis
• Brucellosis

17
Discussion

• Differential Diagnosis - Fever of Unknown Origin
• Rheumatologic
• Lupus
• Systemic JRA
• Pauciarticular JRA
• Other vasculitic syndromes
• Inflammatory bowel disease
• Malignancy
• Ewing Sarcoma
• Leukemia
• Lymphoma
• Soft-tissue sarcomas

18
Discussion

• Differential Diagnosis - Fever of Unknown Origin
• Other
• Central nervous system dysfunction
• Periodic fevers
• Familial dysautonomia
• Drug fever (Feigin)

19
More to the story

• Pt often visits family in Mexico and has a truly
  devoted passion for goat cheese.
• Family uncertain if cheese is pasteurized.
• Several years ago, a 35 yo aunt from Mexico died
  from complications due to an infectious disease
  called Brucellosis.

20
Ah ha!

• Blood cultures drawn x 3 when pt febrile.
• Preliminary results Gram negative coccobacilli
  growing at day 3 of culture.
• 8 day incubation result of 3 blood cultures
  Brucella melitensis

21
Hospital Course, contd.

• Pt started on po Rifampin and Bactrim once prelim
  blood culture known.
• Pt continued to be febrile for 2 days while on
  Rifampin and Bactrim
• So, pt also started on IV Gentamicin to be
  discontinued once the pt defervesced
• Completed 5 day IV Gent course
• Discharged on po Rifampin and Bactrim to complete
  a 6 week treatment course

22
Systemic JRA - our initial suspicion

• Why the confusion?
• -Characteristic fever Daily or BID temp
• elevations to 102 or higher, followed by
  
• rapid falls to normal
• -Characteristic rash evanescent, occurs
  
• at any location and is found most often
  during
• periods of temperature elevation. Small
  lesions
• (1 cm), pale red macules, usually
  nonpruritic. (Schaller)

23
Brucellosis

• AKA Undulant fever, Mediterranean fever or Malta
  fever
• Zoonotic infection
• Bacteria Brucella melitensis, B. abortus, B.
  suis, B. canis, B. ovis, or B. neotomae
• Gram negative coccobacilli
• Source unpasteurized milk products, animal
  tissue or infected aerosolized particles (Everett)

24
Brucellosis

• Chronic granulomatous infection caused by
  intracellular bacteria
• Most common symptoms are nonspecific
• fever, sweats, malaise, anorexia, fatigue,
  arthralgia, weight loss with few objective
  findings on PE (sometimes LAD, HSM)
• Onset abrupt or insidious
• Malodorous perspiration can be pathognomonic
  (Pappas)

25
Brucellosis

• First recognized in British troops stationed on
  the island of Malta where goat milk was commonly
  consumed
• Only 17 countries world-wide claim to be free of
  disease
• Greatest incidence found in the countries of the
  Middle East- Kuwait and Saudi Arabia (Cutler)

26
Brucellosis

• Focal Infectious Complications
• Most common- Osteoarticular sacroiliitis
• GU epididymoorchitis
• Neuro meningitis, neurobrucellosis
• Endocarditis left heart or previously damaged
  valves
• Hepatic abscess (Everett)

27
Brucellosis

• Treatment
• 6 weeks of Bactrim Rifampin /- 14 day course
  of IV Gentamicin for more serious infection or
  complications
• Neurobrucellosis Doxycycline, Rifampin, Bactrim-
  all cross blood-brain barrier (1-19 mo treatment
  course)
• Endocarditis not cured by pharmacotherapy alone,
  need valve replacement several weeks to months
  of antibiotics (Everett)

28
Brucellosis

• Prevention
• Vaccinate domesticated herds/flocks
• Pasteurize milk

29
Hindsight is 20/20

• What could we have done differently
• -Initially taken a more extensive history
• Dietary history
• Detailed family history
• -Sent additional stool for ova/parasites
• -Obtained LFTs since had c/o abd pain and
  hepatic abscess can be complication of
  Brucellosis
• -Echocardiogram r/o endocarditis/Brucellosis
  complications
• -Considered the use of Doxycycline in place of
  Rifampin due to literature citing Doxy as having
  improved efficacy when treating Brucellosis
  (Roushan)
• -Remember Brucellosis is in the DDx of FUO with
  a rash.

30
References

• Everett, E Dale. "Brucellosis in Children."
  UpToDate. 13 July 2006. 26 Feb 2007
  lthttp//www.uptodate.comgt.
• Everett, E Dale. "Microbiology, epidemiology, and
  pathogenesis of Brucella." UpToDate. 16 August
  2006. 26 Feb 2007 lthttp//www.uptodate.comgt.
• Feigin, Ralph D, Palazzi, Debra L. "Etiologies of
  fever of unknown origin in children." UpToDate.
  18 October 2005. 26 Feb 2007 lthttp//www.uptodate.
  comgt.
• Schaller JG. Juvenile rheumatoid arthritis.
  Pediatrics in Review. 18(10)337-49, 1997 Oct

31
References, continued

• Roushan MR., Gangi SM., Ahmadi SA. Comparison of
  the efficacy of two months of treatment with
  co-trimoxazole plus doxycycline vs.
  co-trimoxazole plus rifampin in brucellosis.
  Swiss Medical Weekly. 134(37-38)564-8, 2004 Sep
  18.
• Pappas G., Akritidis N., Bosilkovski M., Tsianos
  E., Brucellosis. New England Journal of
  Medicine. 352(22)2325-36, 2005 Jun 2.
• Cutler SJ., Whatmore AM., Commander NJ.
  Brucellosis--new aspects of an old disease.
  Journal of Applied Microbiology. 98(6)1270-81,
  2005

32
The End