Case 2: JS

1
Case 2 JS

• 60 year old white male
• Multiple medical problems including Type 2
  diabetes mellitus, hypertension, bilateral renal
  artery stenosis requiring repeat angioplasty and
  stent placement, renal insufficiency
• Underwent repeat renal artery angioplasty 1/29/2
  complicated by post-procedure fever

2
Case 2 JS

• After discharge, fever continued intermittently
• Presented to OSH ED with T 102o 2/1/2 and was
  admitted for further evaluation of fever
• Empiric antibiotic coverage initiated on
  admission with ceftriaxone and levofloxacin
• 24 hours after admission, fever persisted and
  patient developed papular rash
• Antibiotic coverage changed to Vancomycin,
  ciprofloxacin

3
Case 2 JS

• Evaluation included routine laboratory studies,
  blood and urine cultures, CXR, abdominal U/S,
  TTE. Studies unrevealing.
• Patient transferred to NCBH 2/5/2 for further
  evaluation of fever.
• On arrival, antibiotics held.
• Cultures, CXR repeated and unrevealing.
• Admission WBC 9.1 with 78 PMNs, 11 eosinophils

4
Case 2 JS

• Fever persisted
• TEE performed LVH, ? vegetation
• Infectious diseases consulted re
  undifferentiated fever

5
Case 2 JS

• Additional history obtained.
• Rare chills, ROS otherwise negative
• No recent travel
• Denied exposures
• Up to date on immunizations
• Current medications ASA, diltiazem, clonidine,
  methyldopa, lisinopril, furosemide, atorvastatin,
  glipizide XL
• Only new medication methydopa (Aldomet)

6
Case 2 JS

• Physical examination VS T 101.9 BP 169/78
• Gen Pleasant obese wm NAD
• HEENT Conj pink Sclera non-icteric OP clear
• NECK Supple ?LAD Carotid 2 B ?bruit
• CHEST CTA CV RRR II/VI SEM apex
• ABD bs NT/ND palpable liver edge ? aud renal
  bruits
• BACK ?CVA tenderness, bruising
• EXT ?c/c/e R groin cath site clean ?ecchymoses,
  induration
• SKIN resolving papular rash over abdomen and back

7
Case 2 JS

• Labs included nl WBC (6.8) with 88 segs, HGB
  9.0, Cr 2.1, nl TSH, alk phos 212, AST 24, ALT
  34, CRP 38
• Differential diagnosis included
• Angioplasty related infected pseudoaneurysm,
  hematoma, cholesterol emboli
• Drug hypersensitivity

8
Case 2 JS

• Recommended
• Holding methyldopa
• ?ANA, anti-histone antibiodies
• CT scan abd/pelvis
• CT scan unrevealing
• Next afternoon patient defervesced. Remained
  afebrile.
• D/C home presumed Aldomet hypersensitivity

9
Methyldopa Drug Fever

• Drug fever is a relatively common adverse effect
  of methyldopa
• Most cases have occurred within 1 to 2 weeks of
  initiation of therapy
• Fever as high as 40 degrees Centigrade has been
  reported.
• All patients have recovered following
  withdrawal of the medication

10
Methyldopa

• Drug fever from the use of methyldopa appears in
  about 1 to 3 of the patients (Dukes, 1992).
• It may appear as soon as 2 days up to 8 weeks
  after initiation of therapy with average time of
  onset ? 10 to 20 days (Glontz Saslaw, 1968).

11
Methyldopa

• Symptoms seen are sudden onset of spiking fevers
  (100 to 105 F have been reported), chills,
  myalgias, general
  malaise, non-productive cough, diaphoresis, and
  rarely, skin rashes and central nervous system
  manifestations (ie, confusion and agitation)
  (Mainzer, 1980 Tallgrun Servo, 1969).
• Eosinophilia and an elevated sedimentation rate
  may be seen.
• Liver function abnormalities reported frequently

12
Methyldopa

• The mechanism appears allergic in nature
• doses as low as 250 mg daily have produced drug
  fever (Furhoff, 1978)

13
Methyldopa

• Stanley et al. (1986) reviewed 78 cases of drug
  fever induced by methyldopa
• Onset was within 5 weeks of initiation of therapy
  (mean 11 days)
• Resolution occurred within 48 hours of stopping
  methyldopa
• Drug fever was not found to be dose-related.
• Eosinophilia and skin rash not present in this
  cohort.

14
Methyldopa and SLE

• Methyldopa has been implicated in inducing
  positive antinuclear antibody (ANA) tests in 13
  to 53 of patients (Dukes, 1980)
• Patients presenting with SLE-like illness have
  received doses of methyldopa ranging from 250mg
  to 1 g/day for gt3-4 months

15
Methyldopa and SLE

• Clinical presentation of a SLE-like syndrome due
  to methyldopa is rare.
• Most patients who develop positive ANA titers do
  not fulfill criteria for SLE.
• Recovery after drug withdrawal and supportive
  treatment reported by Nordstrom et al, 1989.

16
Methyldopa and SLENordstrom DM. West SG. Rubin
RL. Methyldopa-induced systemic lupus
erythematosus. Arthritis Rheumatism.
32(2)205-8, 1989 Feb.

• 55-year-old male with hypertension developed
  syndrome c/w SLE following 13 months of
  methyldopa therapy (250 mg orally twice daily)
• Presented with arthritis, myalgias, hemolytic
  anemia, photosensitive rash, and a positive ANA
• The induced antinuclear antibodies were
  primarily IgG directed against class
  H(1) histones. Anti-dsDNA (-).

17
Methyldopa and SLENordstrom et al. cont.

• Methyldopa discontinued. Therapy with Prednisone
  initiated
• Symptoms, including hemolytic anemia, resolved
  completely.
• Patient recovered without sequelae, and no
  recurrence of symptoms at 2-year follow-up

18
Case 2 JS

• ANA, anti-histone antibodies (-)
• Patient remained afebrile off methydopa,
  antibiotics