Paradoxical Reaction of Raynaud Phenomenon following the Repeated Administration of Lloprost in a Patient with Diffuse Cutaneous Systemic Sclerosis

Objective TO report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. Case Summary In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5–1 ng/kg/min (6 hours per day, for 5 days every 6–8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Discussion Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. Conclusions This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

Hypersensitivity Syndrome and Pure Red Cell Aplasia Following Allopurinol Therapy in a Patient with Chronic Kidney Disease

OBJECTIVE: To report a rare case of combined hypersensitivity syndrome and pure red cell aplasia (PRCA) following allopurinol therapy. CASE SUMMARY: A 43-year-old woman with underlying mesangioproliferative glomerulonephritis developed fever, generalized morbilliform rash, leukocytosis with marked eosinophilia, and hepatic dysfunction 3 weeks after starting allopurinol therapy (300 mg/day for 3 days followed by 200 mg/day) for hyperuricemia and arthritis. The clinical findings were judged to be a probable drug reaction according to the Naranjo probability scale. The drug-induced hypersensitivity syndrome (DHS) resolved after withdrawal of allopurinol and initiation of systemic corticosteroid therapy. However, there was progressive worsening of anemia with reticulocytopenia; PRCA was suspected. PRCA was judged to be a possible drug reaction according to the Naranjo probability scale. The patient refused blood transfusion and bone marrow biopsy. Recombinant human erythropoietin was initiated in addition to prednisolone 15 mg daily. Eleven days later (~7 wk after allopurinol withdrawal), both the hemoglobin level and reticulocyte count began to rise. The patient consented to a bone marrow study at that time, which confirmed the presence of dysplasia involving only the erythroid lineage. DISCUSSION: Allopurinol may induce DHS, aplastic anemia, and, in rare instances, PRCA. We report the first case of PRCA concurrent with allopurinol-induced DHS in a patient with chronic kidney disease. Discontinuation of allopurinol is the first step in the treatment of such cases. The slow recovery of PRCA might be partly attributed to her underlying chronic kidney disease. CONCLUSIONS: To minimize serious DHS, proper indications for treatment and dosage adjustment should be closely observed when starting allopurinol therapy in patients with chronic kidney disease.

Pseudodementia Associated with Use of Ibuprofen

OBJECTIVE To report a case of dementing syndrome resulting from ibuprofen use. CASE SUMMARY A 76-year-old white man with normal mental status became confused, was lost in familiar places, and showed short-term memory loss after beginning a therapeutic regimen of ibuprofen 600 mg 3 times daily for osteoarthritis in anticipation of embarking on a foreign trip. Symptoms of dementia began within 1 week after taking ibuprofen and resolved completely within 1 week after the ibuprofen regimen was stopped. This pattern was repeated 6 months later, when the patient again traveled abroad. Consistently before, during, and after these events, the patient took atenolol, clonidine, lisinopril, aspirin, vitamin C, lecithin, vitamin E, and multivitamins. DISCUSSION Using the Naranjo probability scale, we reasoned that the patient's dementia-like syndrome could be attributed to the use of ibuprofen because pseudodementia appeared after the suspected drug was administered, improved when the drug was discontinued, reappeared when the drug was readministered, had no apparent alternative cause, manifested similarly after each exposure to ibuprofen, and was confirmed by the family's observation after both episodes. Objective causality assessment revealed that the adverse drug reaction was probable. CONCLUSIONS Use of ibuprofen must be considered during clinical evaluation of any patient with new onset of dementing illness. The Naranjo probability scale may be clinically useful for evaluating other pharmaceutical agents that may be contributing to development of dementia-like conditions.