Cocaine, a positive ANCA and Mycophenolate Mofetil'

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Cocaine, a positive ANCA and Mycophenolate
Mofetil.

• FC van Wyk, A Toma, P Kiely.

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Case Report E.B. 42 yo Female

• 2005
• Loss of energy, nasal crusting, epistaxis and
  right facial pain.
• Weight loss, fevers and drenching night sweats.
• Nasal cocaine use for 3 years, daily for the last
  year.
• O/E Large nasal septal perforation and necrosis
  of nasal and sinus mucosa.

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continued

• Microbiology
• Heavy S. aureus.
• Blood results revealed a ESR 65, CRP 88.7, ACE
  normal
• cANCA positive, PR3 and MPO negative.
• Histology
• mixed inflammatory cell infiltrate, including
  eosinophils
• no evidence of granuloma or vasculitis,
• but a great deal of necrotic tissue.

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Initially Rx as case of atypical Wegeners

• High dose steroids, Methotrexate and
  Co-amoxyclav.
• Facial pain, night sweats and malaise improved.
• At five months
• Continued cocaine use, but reduced her
  consumption by 50.
• Prednisolone at 17.5mg daily.
• Methotrexate stopped, Cyclophosphamide started.

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At eleven months

• Cushingoid.
• Requiring 12.5 to 15mg of prednisolone daily
• to keep facial pains, malaise, fever and anorexia
  at bay.
• Cocaine free for 5 months
• Commenced Mycophenolate Mofetil (MMF) 500mg bd.

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Six weeks after MMF started

• Felt considerably better
• Far less facial pain, night sweats and fevers.
• Prednisolone was reduced and eventually stopped.
• Two years later she remains in clinical and
  serological remission despite occasional cocaine
  use.

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Lesson 1 Cocaine Induced Midline Destructive
Lesion

• Affects less than 5 of users
• Similarities to Wegener's
• Facial pain
• Epistaxis
• NO
• Systemic features
• C or P ANCA positive (72)
• BUT
• Spares the lungs and kidneys.
• Widespread destruction in the nose
• ANCA target antigen MPO or Human Neutrophil
  Elastase
• Non specific inflammation/necrosis rather than
  granulomas

HMC-1/PR3-ANCA
HMC-1/HNE-ANCA
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Anatomic sites involved in CIMDL and Wegeners
M Trimarchi, G Gregorini, F Facchetti, et al,
Medicine, 80 (2001) 391-404
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Lesson 2 Mycophenolate Mofetil (MMF) may be
useful in resistant cases

• Conservative management usual
• Cessation of cocaine use
• High dose steroids in selected cases
• Control of symptoms and disease progression
• MMF may have adjunctive role
• Immune suppressant
• Prevents proliferation of T and B Lymphocytes
• Used in Myasthenia Gravis, MS, immune
  neuropathies, SLE, Vasculitis, RA and Myositis.

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In Summary

• Cocaine Induced Midline Destructive Lesion
  (CIMDL)
• High incidence of a positive ANCA.
• Mycophenolate Mofetil (an immunosuppressant) may
  be helpful.

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• References
• 1. JC Smith, A Kacker, VK Anand. Midline nasal
  and hard palate destruction in cocaine abusers
  and cocaine role in rhinologic practice. Ear
  Nose Throat Journal 2002813.
• 2. Trimarchi M, Gregorini G, Facchetti F et al.
  Cocaine-Induced Midline Destructive Lesions.
  Medicine 200180391-404
• 3.Trimarchi M, Miluzio A, Nicolai P et al.
  Massive apoptosis erodes nasal mucusa of cocaine
  abusers. Am J Rhinol 200620160-164
• 4.Wiesner O, Russell KA, Lee AS et al.
  Antineutrophil cytoplasmic antibodies reacting
  with human neutrophil elastase as a diagnostic
  marker for cocaine-induced midline destructive
  lesions but not autoimmune vasculitis.
  Arthritis-Rheum 2004502954-2965

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Thank you.
Acknowledgements Dr. Patrick Kiely Mr. Abbad
Toma Mr. Hamid Daya
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• Wegeners Granulomatosis
• Multisystem/organ disease with systemic illness
• Nasal destruction initially mild limited to
  nasal septum in majority
• Necrotising granulomatous inflammation and
  vasculitis
• Combinations of
• cANCA/PR3 or
• pANCA/MPO
• Rarely cANCA/MPO

• CIMDL
• No involvement of non-ENT organs
• At presentation extensive nasal destruction.
• Vascular histology consistent with WG, but
  no extravascular
  granulomas, multinucleated
• giant cells.
• Up to 72 ANCA , but atypical patterns,
• PR3 or human elastase

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Cocaine

• Cocaine is derived from the leaves of the coca
  plant (Erythroxylum coca or E. novagranatense)
  found in South America.
• UK - 200 000 or more problematic users.
• British Crime Survey has shown Cocaine users have
  doubled since 1998.

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Cocaine dependence

• Mechanisms for damage in the nose include
• Vasoconstrictive effect
• Irritant effect of adulterants in the preparation
• Direct trauma from cocaine crystals sniffed at
  high velocity
• Recurrent nasal infections, especially
  staphylococcal

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Lesson 1 A positive c-ANCA does not equal
Wegeners Granulomatosis.

• CIMDL ANCA IIF(c- or p-) positive in 72.
• ANCA directed against human neutrophil elastase
  in 28 to 84, compared with 0 in WG.
• CIMDL affects less than 5 of cocaine users.
• Pathogenesis is unknown, but thought to be
  multifactorial.
• The mechanism may be an enhancing effect on
  apoptosis, with abundant caspase 3 9 expression.

M Trimarchi, G Gregorini, F Facchetti, et al,
Medicine, 80 (2001) 391-404