Background/Purpose

Malignant atrophic papulosis (MAP) is an obliterative vasculopathy which presents with distinctive cutaneous lesions but can progress over months to years to systemic disease with a rapidly fatal course.  Pathologic findings of involved tissues reveal dense deposition of membrane attack complex (MAC).  Eculizumab is a monoclonal antibody which prevents activation of C5 to C5b and C5a.  Within the past five years, based on immunopathology of the disease, eculizumab has been used in MAP.  The relative importance of inhibition of formation of C5a and of inhibition of formation of MAC has not been determined.

Methods

A literature review and personal communication with physicians treating MAP patients throughout the World identified survivors and treatment failures (deaths).  We attempted to identify those characteristics which distinguished the survivors from those who died. 

 

Results  

 We identified eight patients who were treated with eculizumab at different stages of disease and in different circumstances.  Among those eight patients, only three are alive, two for nearly five years since initiation of eculizumab.  Two out of the three survivors presented with GI perforations and cardiovascular decompensation and were placed on eculizumab with an immediate and dramatic response.   They did not receive systemic steroids.    The third live patient presented with CNS involvement affecting the right eye requiring enucleation.  Treprostinil was started after that event, temporarily suppressing cutaneous lesions, but because of gastrointestinal disease progression, eculizumab was later added.  All other patients had received high doses of systemic steroids and may have had bacteremia at the time of treatment with eculizumab.  In addition, one patient had very aggressive dermatomyositis overlap.

Conclusion

Our results suggest that eculizumab is a vital treatment option for patients with rapidly progressive systemic MAP.  These individuals have a life expectancy of less than one year if left untreated.  Treatment benefits likely arise both from the inhibition of C5a formation and from inhibition of formation of membrane attack complex.   Treatment experience to date has been associated with high mortality, which we feel most likely is the consequence of increased risk of bowel perforation and septicemia in those who had already received systemic steroids.   The avoidance of systemic steroid therapy is essential for a good outcome.  Also, earlier identification of those at high risk for bowel perforation should improve outcome by reducing risk of bacteremia developing during treatment.   We report long term survival of several individuals, but in none was eculizumab effective long-term as monotherapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/eculizumab-treatment-of-malignant-atrophic-papulosis-kohlmeier-degos-disease-world-experience-to-date/