A RASH

1
A RASH?

• AIM Conference
• 5/14/03

2

• 64 yo WM with COPD, Afib, DM, CHF (EF-20), PVD
  who presents with new rash.
• Pt recently discharged 3 weeks earlier with CHF
  exac. and Afib RVR.
• Started on Coumadin, Plavix, and Amiodarone.
• Pt returns to ED 2 weeks after discharge with
  non-blanchable macules and papules all over the
  body.
• Dx Vasculitis secondary to Plavix

3

• Pt returns to PCP clinic 3 weeks after d/c with
  worsening rash
• Purpuric bullous/necrotic lesions on legs and
  feet
• Pt has CRI with Cr 1.5-2. Pt now with
  microscopic hematuria and proteinuria.
• BC MSSA
• Chest CT- LLL PNA, small L pleural effusion

4

• Meds
• NPH/Regular Insulin
• Prednisone
• Ambien
• Combivent
• Advair
• Cardizem CD

• Meds
• Amiodarone
• Plavix
• Coumadin
• Lotensin
• Digoxin
• Lasix
• Aldactone

5

• PE
• Gen Lethargic
• Lungs CTAB
• Heart RRR No M/R/G
• Skin Multiple areas of palpable/nonpalpable
  purpura. Large necrotic ulcers on feet

6

• Labs
• Na-132, K-4.4, CO2-24, BUN-1.8, Cr-1.8, Glc-100
• WBC-6.1, Hgb-9.7, Hct-29, Plt-174
• ANA-, HIV
• WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?

7

• Paraneoplastic or malignancy-associated form of
  vasculitis frequently due to a lymphoproliferative
  disease
• Wegener's granulomatosis
• Polyarteritis nodosa (including that due to
  hepatitis B)
• Microscopic polyarteritis
• Henoch-Schönlein purpura
• Cryglobulinemia (Due to Hep C)
• Idiopathic cutaneous vasculitis
• Hypersensitivity vasculitis

8

• Biopsy
• Early Leukocytoclastic vasculitis (LCV)
• LCV- Acute necrotizing inflammation of the small
  caliber vessels in the upper dermis.
• Most commonly encountered vasculitic
  manifestation in clinical practice
• Palpable purpura, necrotic papules, ulcerative
  lesions

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Hypersensitivity vasculitis

• Age gt16
• Use of a possible offending drug in temporal
  relation to the symptoms
• Palpable purpura
• Maculopapular rash
• Biopsy of a skin lesion showing neutrophils
  around an arteriole or venule

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Hypersensitivity vasculitis

• The presence of three or more of these criteria
  had a sensitivity and specificity for the
  diagnosis of hypersensitivity vasculitis of 71
  and 84 percent, respectively.

11
What drugs do you want to stop and do you treat?
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• Meds
• NPH/Regular Insulin
• Prednisone
• Ambien
• Combivent
• Advair
• Cardizem CD

• Meds
• Amiodarone
• Plavix
• Coumadin
• Lotensin
• Digoxin
• Lasix
• Aldactone

13

• Which drugs do you stop?
• 10-20 of dermal reactions to drugs are
  vasculitic
• Interval between first administration and
  development between vasculitis is extremely
  variable (Hours to years)

14

• Most information about drugs is from case reports
• Little data to show recurrence of vasculitis with
  rechallenge of drug
• May be dose-dependent response
• Complete resolution in most patients (Resolution
  in 1-4 weeks)
• UpTodate includes amiodarone, benazepril, lasix,
  spironolactone, warfarin, and diltiazem as drugs
  that can cause a hypersensitivity vasculitis

15
Holder S., Joy M., Falk R. Cutaneous and
Systemic Manifestations of Drug-Induced
Vasculitis. Annals of Pharmacotherapy 2002 36
130-147.

• Medline search from 1965-99 focusing on drugs and
  vasculitic reactions
• English articles
• Difficult to interpret types of vasculitis before
  1994 Chapel Hill Consensus Conference

16
Holder S., Joy M., Falk R. Cutaneous and
Systemic Manifestations of Drug-Induced
Vasculitis. Annals of Pharmacotherapy 2002 36
130-147.

• Top Ten Drugs
• PTU
• Hydralazine
• G-CSF
• Cefaclor
• Minocycline

• Allopurinol
• D-penicillamine
• Phenytoin
• Isotreitnoin
• Methotrexate

17
Holder S., Joy M., Falk R. Cutaneous and
Systemic Manifestations of Drug-Induced
Vasculitis. Annals of Pharmacotherapy 2002 36
130-147

• Furosemide
• 3M, 2F. Cutaneous and renal involvement
• 1 death
• Coumadin
• 2M. Cutaneous involvement only
• No deaths
• Diltiazem
• 1M, 4F. Cutaneous and hematologic involvement
• All resolved
• All ACE inhibitors
• 8M, 3F. Cutaneous and renal involvement
• 3 deaths

18
Scharf C. Clinical picture Amiodarone-induced
pulmonary mass and cutaneous vasculitis. Lancet
2001 358 2045.

• 67 yo m with CHF presents with hemoptysis and
  macular erythema on both legs.
• Pt on quinapril, digitalis, furosemide,
  phenprocoumon, and amiodarone
• Lung CT RUL pulm mass with necrosis
• Skin bx Lymphocytic vasculitis of small
  capillaries
• Dx Amiodarone induced pulmonary mass and
  cutaneous vasculitis
• Resolution of mass in 4 months after stopping
  amiodarone

19
Mandrup-Poulsen T. Leukoctyoclastic vasculitis
induced by SC injection of human insulin in a
patient with Type 1 Diabetes and Essential
Thrombocytopenia. Diabetes Care 2002. 25
242-243.

• 48f with type 1 DM developed nodules.
• Pt recently switched from semisynthetic insulin
  to recombinant insulin.
• Bx Leukocytoclastic vasculitis
• Pt tried switching insulins and insulin pumps
  without success
• ID skin testing to human, porcine, and bovine
  insulin but no reactions to protamine or other
  additives
• Pt treated with prednisolone and azathioprine
• Vasculitis resolved and pt continued on
  recombinant regular and NPH insulin

20

• Churg-Strauss associated with Fluticasone
• Simon J. Churg-Strauss Syndrome associated with
  fluticasone therapy. Archives of Dermatology
  2001. 137.
• Hypersensitivity reaction associated with
  Clopidogrel.
• Sarrot-Reynauld. Severe Hypersensitivity
  associated with clopidogrel. Annals of Internal
  Medicine 2001. 135 305-306.

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• Normal Labs ANCA, Prot C S, Acute and Chronic
  Hepatitis, Cardiolipin IgM IgA, C3, C4, SPEP
• No vegetations on TEE
• Tx Prednisone 60mg qd and stopped Lasix,
  Spironolactone, and Coumadin
• Pt leukocytoclastic vasculitis continues to
  improve