Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists.

[Diclofenac induced liver injuries]. / CME-Klinische Pharmakologie: Diclofenac-induzierte Leberschäden.

We report the case of an 83-year-old female patient who developed diclofenac-associated liver injury nine days after therapy had started. Diclofenac was used to treat back pain associated with an acute exacerbation of a chronic lumbovertebral symptoms reversed. We discuss the adverse reaction profile of diclofenac, particularly diclofenac-induced liver injury. We also discuss the epidemiology, clinical presentation and mechanisms of NSAID-induced liver injury, as well as risk factors and preventive measures.

[Severe pancytopenia and stomatitis in a patient treated with low-dose methostraxate]. / Schwere Panzytopenie und Stomatitis unter low-dose-Therapie mit Methotrexat.

A 68-year-old female patient presented at the emergency room with episodes of epistaxis, dysphagia and malaise. The patient had acute prerenal renal failure, probably in association with previous infection of the airways and treatment with NSAID's. Laboratory values revealed greatly decreased leukocyte and platelet counts as well as anemia. The patient had a diagnosis of a seronegative arthritis since 9 months and, therefore, was treated with low dose methotrexate (MTX) 10 mg/week. After exclusion of other causes, myelosupression was considered to be associated with low-dose MTX. After stopping MTX and treatment with folic acid leucocyte and platelet counts returned to normal and stomatitis recovered as well within nine days. We discuss the pharmacology of low-dose MTX and in particular the risk factors and prophylaxis of its toxicity. Renal function needs special attention in patients treated with low-dose MTX.

[Rhabdomyolysis associated with atorvastatin combined with amiodarone and fluconazole]. / Rhabdomyolyse unter der Kombination Atorvastatin, Amiodaron und Fluconazol.

A 67-year old man was hospitalized due to an aorto-coronary bypass and cecal perforation. After administration of atorvastatin, amiodarone, and fluconazole, rhabdomyolysis developed with electrolyte disturbances (hyperphosphatemia, hyopcalcemia) and a massive increase in creatine kinase and myoglobin. In the clinical course, other complications manifested such as acute renal failure, critical illness myopathy, acute gout on the knee, and sternal infection with coagulase-negative staphylococci. After stopping the assumed causal agents and treating the complications, the patient could be transferred for rehabilitation after a more than two months hospital stay. We discuss the causes and symptoms of muscle diseases as well as the epidemiology, mechanisms, treatment, and prevention of drug-induced myopathies with a focus on statins.

[Rash, fever, eosinophilia and elevated liver enzymes. DRESS syndrome (drug reaction or rash with eosinophilia and systemic symptoms)]. / Exanthem, Fieber, Eosinophilie und erhöhte Leberwerte. DRESS syndrome (drug reaction or rash with eosinophilia and systemic symptoms).

We report on a patient with Pneumocystis jirovecii pneumonia who developed fever, rash, eosinophilia and hepatitis 10 days after initiation of a therapy with sulfamethoxazole and trimethoprim. A DRESS syndrome was diagnosed and the therapy was changed successfully to pyrimethamine and dapsone. We describe the clinical picture, causative drugs, pathogenesis, differential diagnoses and therapy of this life-threatening disease to acquaint the general practitioner with it.

[Lamotrigine and the skin]. / Lamotrigin und die Haut.

We report a patient with personality disorder and depression who developed a reversible macular rash 10 days after starting lamotrigine (LTG). We discuss the safety profile of LTG, risk factors for adverse reactions of the skin, the management of risk reduction of LTG - induced skin reactions and the possibility of a controlled reexpostion of patients with benign LTG - associated rash.

[Unexpected loss of therapeutic effect of oxcarbazepine]. / Ungewöhlicher Wirkungsverlust von Oxcarbazepin.

After months of successful analgesic therapy with oxcarbazepine, a 52-year old woman with trigeminal neuralgia suddenly experienced episodes of heavy trigeminal attacks regularly in the evening at about the same time. Asked about changes in daily life or eating habits, she reported the ingestion of healing earth daily in the morning. After stopping the ingestion of healing earth, analgesic control of trigeminal neuralgia was restored without any changes of the initial pharmacotherapy. In daily practice, interactions which significantly influence the absorption of drugs are often overlooked. The documentation of these interactions in drug interaction databases, in the prescribing information, and in the literature is sparse though clinically relevant. Separating the ingestion of interacting substances by a time interval may not sufficiently avoid the interaction in every case. Particular caution is warranted when slow-release cation containing drugs or substances with entero-hepatic circulation are used.

[Zoledronate-associated end stage renal failure and hypocalcaemia]. / Zoledronat-assoziierte terminale Niereninsuffizienz und Hypokalzämie.

In an 81-year-old patient with a history of long-standing stable chronic renal failure a diagnosis of multiple myeloma was made. After an initial chemotherapy, a therapy with intravenous pamidronate, 90 mg monthly, was initiated. After four years of well tolerated therapy, pamidronate was stopped and zoledronate, 4 mg intravenously every four weeks, was started. After approximately one year, an elevated plasma creatinine was noted for the'first time, progressing to end stage renal failure within the next months. At admission, besides end-stage renal failure, severe asymptomatic hypocalcemia was noted. Renal biopsy findings included severe tubulointerstitial damage compatible with drug-induced tubular injury. Prerenal and postrenal failure could be excluded as well as myeloma kidney. The diagnosis of zoledronate-associated end-stage renal failure was made and treatment with hemodialysis was started. Hypocalcemia was treated with calcium and vitamin D3 supplements. After two years of follow up, the patient still required hemodialysis.

[Minocycline-induced lupus erythematodes]. / Minocyclin-induzierter Lupus erythematodes.

We report the case of an 18-year-old woman with arthralgia and swelling of distal joints at hands and feet, photosensitive reaction, butterfly rash, fatigue, tachypnea and unspecific cardiac pain three months after beginning a treatment with minocycline for acne. Recurrence of symptoms at a higher intensity occurred within hours of reexposition with minocycline. The antinuclear antibody test was positive. After withdrawal of minocycline, the symptoms improved and minocycline-induced lupus was diagnosed. In the Swissmedic and WHO adverse drug reaction databases 267 other cases of possible minocycline-induced lupus were identified. Typical clinical and laboratory features are arthralgia, arthritis, myalgia, increased transaminases and/or jaundice, unspecific symptoms like fatigue and fever, skin disorders and positive antinuclear antibodies.

[Prevalence of potential drug-drug interactions in ambulatory patients with statin therapy]. / Prävalenz potentieller Arznei- mittelinteraktionen bei ambulanten Patienten unter Statin-Therapie.

AIM: To asses the prevalence of potentially critical drug-drug interactions (DDIs) in outpatients treated with a statin. PATIENTS/METHODS: Data of patients (e.g. age, sex, comorbidities, individual statin, number of drugs, number of diagnoses) were collected from 242 Swiss practitioners. The medication was screened electronically for potentially critical DDIs. RESULTS: We included 2742 statin-treated patients (mean age 65.1 +/- 11.2 [SD] years, 3.2 +/- 1.6 diagnoses, 4.9 +/- 2.4 drugs prescribed) from the German (53.3%), French (36%) or Italian speaking (10.7%) part of Switzerland. Of those, 401 (14.6%) had a total of 591 potentially severe DDIs; 190 patients (6.9%) had potential statin DDIs, 288 (10.5%) potential non-statin DDIs, mainly due to pharmacodynamic mechanisms. The prevalence of potential DDIs was similar between regions, except for a trend for a higher prevalence of drug-statin interactions in the French-speaking part. The number of drugs per patient and a diagnosis of arrhythmia or heart failure were identified as risk factors for DDIs. CONCLUSIONS: Drug combinations with potentially severe DDIs are common in patients treated with statins due to pharmacotherapy of their co-morbidities. Special attention in this specific population should be drawn on patients with polypharmacy and those with drug treatments for arrhythmia or heart failure.