Opioid associated intravenous and cutaneous microvascular drug abuse (skin-popping) masquerading as Degos disease (malignant atrophic papulosis) with multiorgan involvement.

BACKGROUND: In 2012, a nephrologist reported the development of a multiorgan thrombotic syndromic complex resembling thrombotic thrombocytopenic purpura (TTP) in patients who were abusing long acting oxymorphone hydrochloride; all patients had hemolytic anemia and thrombocytopenia. OBJECTIVE: Herein, we report another case involving a 31-year-old woman who self intravenously administered dissolved oral oxymorphone resulting in thrombotic sequelae resembling Degos disease. METHODS: Formalin-fixed and paraffin embedded skin biopsies were prepared according to standard protocols for H&E and immunohistochemistry. RESULTS: The clinical presentation and biopsy findings were held to be indicative of Degos disease/malignant atrophic papulosis (MAP) but with unusual clinical features including renal failure and severe respiratory insufficiency. Given the efficacy of eculizumab in the treatment of the acute thrombotic phase of Degos disease/MAP, the patient received this drug, resulting in rapid resolution of signs and symptoms associated with her multiorgan failure. Although she developed recurrent cutaneous ulcers despite complete complement inhibition with eculizumab., her other extracutaneous manifestations did not recur. The patient's pre and post eculizumab skin biopsies showed a striking pauci-inflammatory thrombogenic vasculopathy associated with marked endothelial cell injury along with deposits of C3d and C4d within the cutaneous vasculature; the C5b-9 deposits were limited to the pre-eculizumab biopsy. We discovered that her syndromic complex was a self-inflicted one related to the localized administration of dissolved oxymorphone. CONCLUSION: Our patient's biopsy along with the rapid response to eculizumab indicates that this distinct thrombotic microangiopathy is another complement mediated thrombotic microangiopathy syndrome. Opioid thrombotic microangiopathy has a varied clinical presentation and can mimic other catastrophic microangiopathy syndromes, all of which have in common a responsiveness to complement inhibition.

Recurrent Myocardial Infarction Despite Normal C-reactive Protein in a Patient with Behcet's Disease and Compound Heterozygous Methylenetetrahydrofolate Reductase (MTHFR) Mutations (C677T and A1298C).

A 39-year-old diabetic female with Behcet's disease presented with acute inferior wall myocardial infarction and underwent successful angioplasty of the occluded circumflex artery with a bare-metal stent (balancing increased the bleeding risk with Behcet's). Other coronary vessels were free of obstructive atherosclerosis. Optimal coronary artery disease (CAD) therapy was commenced, and Behcet's disease treatment was intensified with the normalization of C-reactive protein. Two years later, she presented with an acute left anterior descending artery occlusion that was managed with a drug-eluting stent this time. There was no evidence of diffuse atherosclerosis on coronary angiogram or coronary calcifications on the chest computed tomography (CT) scan. Compound heterozygous methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and high-normal plasma homocysteine were detected. With the long-term continuation of dual anti-platelet, lipid-lowering, immunosuppressive, and folic-acid therapies, she did not have cardiac events during the three-year follow-up. This is the first report of recurrent thrombotic acute coronary syndrome (ACS) in a patient with diabetes, compound heterozygous MTHFR mutations, Behcet's disease with normal C-reactive protein (CRP), and no evidence of diffuse coronary artery disease.

Effective treatment of malignant atrophic papulosis (Köhlmeier-Degos disease) with treprostinil--early experience.

BACKGROUND: Malignant atrophic papulosis (Köhlmeier-Degos disease; MAP) is an uncommon endotheliopathy with pathological findings similar to the vascular lesions of systemic sclerosis. These two disorders can overlap. When associated with visceral lesions, MAP has been considered almost universally and rapidly fatal. A recent report described dramatic response to treatment with eculizumab, but disease progression after initial response to therapy has occurred. METHODS: We describe the clinical and pathologic findings in two patients, one with MAP and the other with MAP like lesions, who received treatment with subcutaneous treprostinil. One patient had an overlap syndrome with features of systemic lupus erythematosus (SLE) and scleroderma and severe pulmonary hypertension. She also had very extensive MAP like cutaneous lesions. There was no evidence of central nervous system (CNS) disease and laparoscopy revealed no visible MAP lesions on the serosa of the small bowel. The second patient had experienced life-threatening disease progression despite ongoing eculizumab therapy. During this treatment, he had developed CNS and bladder involvement with neurologic symptoms and gross hematuria. RESULTS: Patient one was placed on therapy with treprostinil for her pulmonary hypertension, but in the months subsequent to initiation of treatment, dramatic and complete resolution of cutaneous MAP like lesions and disabling digital pain occurred. In patient two, therapy with treprostinil was temporally associated with clearing of hematuria, resolution of CNS symptoms and improvement in MRI findings. CONCLUSIONS: Treprostinil may offer a second effective treatment approach to individuals with MAP or "rescue therapy" to those in whom eculizumab treatment has failed to maintain suppression of disease activity.