Lower extremity ulcers in connective tissue diseases

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Lower extremity ulcers in connective tissue
diseases
Victoria K. Shanmugam, MD Rheumatology
Fellow Georgetown University Hospital
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CLINICAL PROBLEM

• Leg ulcer incidence
• 1 of general population
• 9 in RA1
• 5.6 in SLE2
• 6.6 of ulcer patients have associated systemic
  autoimmune disease3
• Etiology and impact on quality of life unknown

1Thurtle OA , CawleyMI, J Rheumatol. 1983
10(3)507-509 2Tuffaneilli DL, Dubois EL, Arch
Dermatol. 1964 90377-386 3Goslen JB, Clin
Dermatol. 1990 8(3-4)92-117
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(No Transcript)
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Livedoid vasculopathy
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Livedoid vasculopathy
Purpuric macule
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Livedoid vasculopathy
Purpuric macule
Painful irregular ulcers
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Livedoid vasculopathy
Purpuric macule
Painful irregular ulcers
Stellate porcelain white scars with surrounding
telangiectasia
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Livedoid vasculopathy

• Milians white atrophy
• Atrophie blanche
• Segmental hyalinizing vasculitis
• Livedo reticularis with summer exacerbation
• Livedo or livedoid reticularis
• PURPLE painful purpuric ulcers with reticular
  pattern of the lower extremities

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Livedoid vasculopathy

• Milians white atrophy
• Painful purpuric lesions
• Positive syphilis serology

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Livedoid vasculopathy

• Milians white atrophy
• Painful purpuric lesions
• Positive syphilis serology

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Livedoid vasculopathy

• Milians white atrophy
• Painful purpuric lesions
• Positive syphilis serology

FIBRIN OCCLUSIVE VASCULOPATHY
Milian G., Bull Soc Franc Derm Syph. 1929
36865-871
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Livedoid vasculopathy
Modified from Callen JP., Arch Dermatol. 2006
142(11)1481-82
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Virchows triad
ENDOTHELIAL INJURY
HYPERCOAGULABLE STATE
ABNORMAL BLOOD FLOW
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Treatment of livedoid vasculopathy

• Female predominance attributed to lower venous
  fibrinolytic activity in women
• Phenformin and ethylestranol1
• Enhance fibrinolysis
• Effective treatment of livedoid vasculopathy
• Pentoxifylline2
• Methylxanthine derivative
• Alters blood viscosity and neutrophil adhesion
• Now known to also have effects on fibrinolyis
• Heparin3
• Also profibrinolytic
• Effective in a small number of cases of livedoid
  vasculopathy

1Milstone LM, et al., Arch Dermatol.
119(12)963-969 2Seiffge D, Atherosclerosis 1997
131 (suppl.) S27-28 3Hairston BR, et al, Arch
Dermatol. 2003 139 987-990
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AIMS

• Identify
• Common characteristics of lower extremity ulcers
  in CTD and livedoid vasculopathy
• Features which predict response to therapy

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LOWER EXTREMITY ULCERS ICD-9 CODE 707.1
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EPIDEMIOLOGY
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EPIDEMIOLOGY
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EPIDEMIOLOGY
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EPIDEMIOLOGY
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EPIDEMIOLOGY
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DISTRIBUTION OF LESIONS
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DISTRIBUTION OF LESIONS
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DISTRIBUTION OF LESIONS
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DISTRIBUTION OF LESIONS
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DISTRIBUTION OF LESIONS
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DISTRIBUTION OF LESIONS
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PATHOLOGY
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PATHOLOGY
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PATHOLOGY
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PATHOLOGY
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HYPERCOAGULABLE PROFILE
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HYPERCOAGULABLE PROFILE
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IMMUNOSUPPRESSION
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ANTICOAGULATION
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LIMITATIONS

• Retrospective study
• Limited data may underestimate frequency of
  hypercoagulable abnormalities
• No assessment of impact on quality of life
• No randomized controlled trials of treatment in
  these patients

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CLUE REGISTRY AND LoCAL TRIAL

• CLUE REGISTRY
• Identify frequency of hypercoagulable
  abnormalities in pts with leg ulcers
• Assess impact of leg ulcers on QoL in CTD
• LoCAL TRIAL
• Efficacy of Low molecular weight heparin (LMWH)
  therapy, in conjunction with local wound care,
  compared to wound care alone in patients with
  Connective tissue disease and livedoid
  vasculopathy Associated Leg ulcers.

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CLUE REGISTRY AND LoCAL TRIAL
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STRATIFICATION
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CLUE REGISTRY AND LoCAL TRIAL
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THANK YOU

• Mentors
• Dr. Thomas Cupps
• Dr. Virginia Steen
• Dr. Nancy Lane
• Collaborators
• Dr. Christopher Attinger
• Dr. Blanche Mavromatis
• Dr. Craig Kessler
• Kara Couch
• Dan Lane

• Financial support
• Kay Family Foundation
• ACR Research and Education Foundation