Case Conference January 14, 2001

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Case ConferenceJanuary 14, 2001

• Caryn G. Morse, MD
• Infectious Diseases

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Case MG

• 72 year old white female
• Previously in excellent health
• Transferred from outside hospital for further
  evaluation and management of fever, rash and
  abdominal pain

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Case MG cont.

• According to the patient and her family, patient
  developed symptoms of fatigue and dizziness two
  weeks prior to admission
• Presented to local emergency department where
  evaluation revealed elevated blood pressure and
  U/A c/w UTI
• Patient rxd TMP/SMX DS BID to complete a 7 day
  course and was d/c to home

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Case MG cont.

• Despite TMP/SMX, patient continued to feel weak
  and dizzy
• Over the next two-three days, developed diffuse
  abdominal pain and nausea
• Presented to primary care physician for further
  evaluation

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Case MG

• PCP checks routine blood work including H.
  Pylori. Labs return normal except for H.
  Pylori serology.
• Patient started on PrevPac.
• Diligently takes prescribed medications, TMP/SMX
  and amoxicillin, clarithromycin and Prevacid.
• Feels awful Now too nauseated to eat or drink.
  Quickly becomes too weak to stand.

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Case MG

• Returns to local emergency department
• Admitted for re-hydration
• OSH admission history and physical examination
  remarkable for
• Patient-reported sulfa allergy
• TEMP 102o
• New reddish-purple blotches on left 1st finger

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Case MG OSH

• On admission to OSH,
• TMP/SMX and PrevPac d/cd
• Blood and urine cultures drawn serially
• Empiric antibiotic therapy with ceftriaxone and
  azithromycin initiated
• CXR, CCT, LP, trans-thoracic echocardiogram,
  abdominal U/S all unrevealing

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Case MG cont.

• Despite broad-spectrum coverage, patient
  continued to spike fevers to 102o daily and
  rash developed on both hands and feet
• Transferred at family request for further
  evaluation and management

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Case MG

• Consult team evaluated patient on the morning
  following transfer
• Patient was somnolent but reported improvement in
  abdominal pain and nausea symptoms since transfer
  but felt the blotches on her hands and feet
  were spreading

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Case MG cont.

• PMH HTN, recurrent vaginal infections
• PSH s/p TAH
• ALL TMP/SMX?rash years ago, Biaxin?makes me
  vomit
• FH M?76 of metastatic colon CA, F?81 HTN, CAD, MI

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Case MG Consult PE

• VS T 99.3 P 78 BP 168/90 RR 18 99 RA
• GEN WD/WN elderly white female, fatigued, NAD
• NEURO Oriented x 3 CN II-XII intact Nl strength
  and sensation Gait not tested
• HEENT Conj pink Sclera non-ict OP scant white
  plaques ? Thrush TA non-palp, non-tender
• NECK Supple ? LAD Carotid 2 ? bruit
• CHEST CTA CV RRR ? m/g/r ? JVD
• ABD bs soft NT/ND ? palpable OGM
• EXT ? c/c Trace ankle edema
• SKIN Multiple punctate and confluent purplish-red
  non-blanchable lesions R temple, bilateral
  forearms, hands, calves and feet. Onychomycosis.

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Case MG labs

• WBC 10.3 S 75 L 16 E 1 HGB 11.8 Pltlt 226
• CMP Na 137, K 3.9, Cl 105, CO2 17, BUN 7, Cr
  0.7, albumin 2.3, alk ? 72, AST 20, ALT 17
• ESR 107
• CK 179
• Blood cx (-)

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Case MG

• Differential diagnosis?
• Further diagnostic testing?
• Empiric therapy broad-spectrum antibiotic
  coverage, steroids?

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Case MG

• 72 year old white female with fever and
  progressive purpura
• Differential diagnosis
• Disseminated bacterial infection esp. infective
  endocarditis
• Cutaneous or systemic vasculitis, drug-induced
  vs. idiopathic

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Case MG

• Agreed with empiric antibiotic coverage for
  endocarditis and TEE
• Recommended the addition of vancomycin 1g IV q12h
  to ceftriaxone 2g IV q24h and gentamicin 100mg IV
  q8h
• Agreed with dermatology consult and biopsy
• Recommended rheumatology and vascular surgery
  consults ? cold agglutinins and cryoglobulins

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Case MG

• TEE ? vegetation
• Blood cxs remained negative
• Cold agglutins (-)
• Cryoglobulins (-)
• Rheum labs including complement returned normal
• Skin biopsy neutrophilic vasculitis

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Case MG Skin Biopsy
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Case MG

• Remained afebrile.
• After initial worsening, purpuric lesions began
  to resolve.
• Given negative blood, urine and skin biopsy
  cultures, decisions was made to discontinue
  antibiotics and patient was closely monitored.
• Remained afebrile and continued to improve off
  antibiotics.
• Discharged home.

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Drug-induced vasculitis

• Wide variety of clinical and pathologic
  conditions that are, in general, empirically
  defined and poorly understood. (Calabrese LH and
  Duna GF. Drug-induced vaculitis. Current Opinion
  in Rheumatology 1996 8(1) 34-40.)
• AKA hypersensitivity vasculitis, allergic
  vasculitis, leukocytoclastic vasculitis, serum
  sickness

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Drug-induced vasculitis

• Calabrese and Duna recommended clasification by
• Precipitating agent
• Organ system(s) involved (eg isolated cutaneous,
  CNS, multisystem) and
• Pathology

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Drug-induced hypersensitivity syndrome

• Syndrome is characterized by fever and rash
• Often accompanied by arthralgias, hepatitis,
  lymphadenopathy and hematologic abnormalities

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Drug-induced hypersensitivity syndrome

• Syndrome usually develops 2-6 weeks after a drug
  is first used
• Rash may be morbilliform, bullous or purpuric
  although purpuric rashes should not be palpable
• Skin biopsy reveals nonspecific inflammatory
  changes, not vasculitis

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Drug-induced hypersensitivity syndrome

• Frequent offenders include sulfa drugs,
  allopurinol and antiepileptics
• With discontinuation of the precipitating drug,
  recovery is usually complete
• Case reports suggest recovery may be hastened by
  the use of corticosteroids

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Drug-induced vasculitis

• Clinical picture varies widely from self-limited
  to progressive to fatal
• Poorly defined and described in the literature
• Usually develops within 1-3 weeks of drug
  exposure

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Drug-induced vasculitis

• Clinical expression is diverse
• Predominant target organ is the skin
• Maculopapular rashes are most common, followed by
  palpable purpura

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Drug-induced vasculitis

• Visceral disease includes glomerulonephritis,
  hepatocellular injury and necrosis as well as
  lung, cardiac and CNS involvement
• Appears to be no specific underlying pathologic
  lesion and in most cases vasculitis is not
  identified in the affected tissue
• In most published reports the diagnosis of organ
  involvement was made clinically

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Drug-induced vasculitis

• Majority of reports in the literature come from
  the study of involved skin
• Small-vessel vasculitis is the predominant
  lesion
• Mononuclear and polymorphonuclear predominant
• Non-necrotizing and mononuclear predominant
• Leukocytoclastic

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Drug-induced vasculitis

• Pathogenesis is thought to be immune mediated
• Evidence of circulating immune-complexes include
  detection of
• soluble complexes
• hypocomplementemia
• immune reactant deposition in vessel wall
• Cell-mediated mechanisms also thought to be
  involved

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Drug-induced vasculitis

• Offending agents are numerous and include
  sulfonamides
• Additional agents of interest include AZT, DDI,
  GCSF, interferon alfa

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Drug-induced vasculitis

• Prognosis appears excellent when disease is
  limited to the skin
• Corticosteroids reserved for cases associated
  with more severe cutaneous involvement, prominent
  constitutional symptoms and disseminated disease
• ?Role of NSAIDs, colchicine, anti-malarials,
  dapsone, cyclophosphamide, plasmapheresis?