Drug-induced Dilemma: Angiokeratomas and Decreased Renal Function

Timing is everything, according to the well-worn aphorism. Yet, it certainly proved true when a diagnosis was sought for a puzzling set of signs and symptoms. An 84-year-old woman was referred to our hospital in December 2012, due to the sudden appearance of multiple eruptive hemorrhagic papules on her skin. The patient had a history of atrial fibrillation, coronary artery disease, and chronic renal insufficiency. Her serum creatinine level was about 1.3 mg/dL, and her estimated glomerular filtration rate, according to the Modification of Diet in Renal Disease Study equation, was 39 mL/min. Following coronary bypass surgery, the patient had been treated with phenprocoumon, a coumarin derivative available in Europe. After a bleeding incident, the anticoagulant was replaced with a combination of acetylsalicylic acid and subcutaneous enoxaparin at a therapeutic dosage. Ten days later, skin changes appeared.

Assessment
Upon examination, the patient had hemorrhagic papules ranging from 2-6 mm in diameter on both hands, the lower legs, and oral mucosa, as well as a hematoma on her right elbow (diameter, 6 cm) and left thigh (diameter, 9 cm) (Figure 1). She was in good general condition with no history of trauma and no sign of fever.

All of her coagulation parameters were normal. Results were as follows: platelet count, 351,000 platelets/μl; international normalized ratio, 1.06; partial prothrombin time, 42 seconds; Quick test, 90%; and anti-factor Xa measurement, 0.44 IU/mL (the therapeutic range for heparin treatment). Serum creatinine and urea levels were elevated at 1.7 mg/dL (reference range, 0.5-0.9 mg/dL) and up to 305 mg/dL (reference range, 10-50 mg/dL), respectively. While the hematomas were attributed to a bleeding complication of enoxaparin, we suspected that the skin lesions were due to necrotizing vasculitis. The differential diagnosis also included septic vasculitis and cytotoxic lymphoma.1

Diagnosis
A sample was retrieved via excision biopsy of a papule on the dorsum of the right hand. Histological examination of the specimen revealed intraepidermal erythrocytes and thrombi in dilated vessels lined by endothelial cells. This finding led to a diagnosis of eruptive angiokeratomas (Figures 2 and 3).

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–Stefan Schliep, MD, Franklin Kiesewetter, MD, Miklos Simon, MD, Clemens Grupp, MD, Lucie Heinzerling, MD, PhD, MPH

This article originally appeared in the July 2014 issue of The American Journal of Medicine.