Sunday, July 14, 2013

A potentially lethal disease

presented by Dr Henry Foong
Ipoh, Malaysia

Abstract:  19 yo man with skin lesions and gastro-intestinal infarcts

History: A 19 yr old student presented with multiple discrete mildly pruritic papules on the trunk and thighs of 9 months duration.  It started as papules on the trunk that become enlarged resulting a central depression.  2 months ago, he had severe abdominal pain,  underwent emergency laparotomy and was told he had a "perforated appendix".  The surgeon noted several shallow ulcers on the large and small intestines.  He was worried about typhoid but serology was negative.  

Exam:  Multiple discrete papules/plaques 3-6 mm diameter with a central porcelain white atrophied depression and a raised border on the trunk and thighs.  There was a rim of telangiectasia on the periphery in some of the lesions. No purpura was noted.

Clinical Photos:




Pathology: A skin biopsy was performed.  Biopsy showed an atrophied epidermis with evidence of arteritis in the deeper dermis.  (see below)

Lab: His blood counts and biochemistry was unremarkable.

Diagnosis:  Degos disease (Malignant atrophic papulosis) appears most likely.  Could this some form of cutaneous lymphoma?

Questions:  Have any of our readers seen and treated similar patients? There are only around 200 cases of Degos Disease reported in the literature.  Treatment is difficult and often ineffective.  Aspirin and dipyridamole has been tried to reduce the complications of vessel thrombosis.  Some cases has been associated with connective tissue disease but by and large those with gastrointestinal complications have poor prognosis. IV immunoglobulins and eculizumab has been tried with some success.

Cost Considerations:  
In the U.S.: 

Eculizumab is ~$7000 per dose at low end

A four dose course of IVIG for a 70 kg person at 2 g/kg would cost $25 000-$26 000. Or ~ $21,000 for a 60 kg person. 

While these drugs may be 40% cheaper in Malaysia can your patient's family afford a trial or does the government pick up the cost?

References:
1. Cynthia M. Magro, MD, Jonathan C. Poe, PhD,et. al.  A C5b-9/Interferon-α–Mediated Endotheliopathy Syndrome.  Am J Clin Pathol 2011;135:599-610

2. Scheinfeld N. Commentary on 'Degos disease: a C5b-9/interferon-α-mediated endotheliopathy syndrome' by Magro et al: a reconsideration of Degos disease as hematologic or endothelial genetic disease.  Dermatol Online J. 2011 Aug 15;17(8):6. Excellent discussion and available Free Full Text 

3. Zhu KJ, et al. The use of intravenous immunoglobulin in cutaneous and recurrent perforating intestinal Degos disease (malignant atrophic papulosis) Br J Dermatol. 2007 Jul;157(1):206-7.

Histopath demonstrates an atrophied epidermis with evidence of arteritis in the deeper dermis.








4 comments:

  1. You are correct David in saying this is a rare diagnosis. I have only seen one case many years ago who died from a perforated bowel. Some people believe it is a form of lupus erythematosus but I personally doubt it. We tried high dose steroids in our case but to no avail. The prognosis is not good. The photography of the case is excellent.

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  2. From: el-Azhary, Rokea A., M.D., Ph.D.

    I would suggest a trial of prednisone for the arteritis and an anticoagulant for the vascular occlusion. Dego's can be associated with antiphosphoplipids.

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  3. From Cynthia Magro M.D. Professor, Weill Cornell Medical College, New York.

    I agree completely with the diagnosis of Degos disease. We are continuing to study this fascinating disease. Eculizumab is a very good drug to deal with the acute microthrombotic catastrophic component of Degos disease however there are additional therapies that may be more effective in dealing with the larger vessel occlusive arteriopathy. If you have any skin biopsies I would love to examine the case further. Also Dr. Boehm from the NIH is developing a genetic model for familial Degos disease. It is quite likely that your patient has primary Degos disease.

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  4. From Lee Shapiro MD, Clinical Professor, Albany Medical College, Albany, NY USA

    As Dr.Magro commented, response to eculizumab has been transient in ALL cases in which it has been employed, althought I am also convinced that it can be life-saving therapy in that the effect of eclizumab infusion is dramatic and immediate. The period of response may be only a few months or many, but it has not been sustained in anyone

    We recently published a report on response to remodulin therapy (in Orphanet, April 2013).

    I had a patient with scleroderma and Degos overlap who was placed on remodulin for pulmonary hypertension. Within a few months, her digital Degos-like lesions resolved.

    We speculate that endothelial progenitor cells are severely depleted in Degos (this has not yet been confirmed) and that remodulin rapidly increases the number of these cells (as reported by David Smadja, MD in a PAH population). There certainly could be other mechanisms by which the remodulin could be beneficial.

    Rho kinase pathway inhibition is under investigation as another treatment approach.

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