A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?

BACKGROUND: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most Serious Cutaneous Adverse Reaction (SCAR) often with a fatal outcome. Coronavirus Disease (COVID-19) is caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV2) and is an emergent pandemic for which no cure exist at the moment. Several drugs have been tried often with scant clinical evidence and safety. CASE PRESENTATION: Here we report the case of 78-years-old woman with cardiometabolic syndrome and COVID-19. A multidrug regimen including others hydroxychloroquine, antibiotics, dexamethasone and paracetamol, low-molecular-weight-heparin and potassium canrenoate was started. After almost 3 weeks, the patient started to display a violaceous rash initially involving the flexural folds atypical targetoid lesions and showing a very fast extension, blister formation and skin detachments of approximately 70% of the total body surface area and mucous membranes involvement consistent with toxic epidermal necrolysis (TEN). The ALDEN algorithm was calculated inserting all drugs given to the patient in the 28 days preceding the onset of the skin manifestations. The highest score retrieved was for hydroxychloroquine. Other less suspicious drugs were piperacillin/tazobactam, ceftriaxone and levofloxacin. CONCLUSIONS: To our knowledge, this is the first case of TEN in a patient suffering from COVID-19 probably associated with hydroxychloroquine. Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.

Aortic dissection after ramucirumab infusion.

A female patient in her seventies affected by a signet-ring cell carcinoma G3pT4N3 (24/29), with lymphovascular invasion, HER2-negative. After completing three cycles of first-line systemic treatment in combination with cisplatin (CDDP) + 5-fluorouracil (5FU), a new systemic therapy line with paclitaxel + Cyramza (ramucirumab) was planned. On the day after the first administration the patient manifested a Standford type A aortic dissection (AD), with a diameter of around 6.5 cm and dissection flap originating in the ascending aorta below the brachiocephalic trunk, extended to the whole descending aorta until the carrefour. The causal relationship between adverse drug reactions and Cyramza, calculated using the Naranjo algorithm, led to a result of 'probable' correlation between ramucirumab and AD. The endothelial dysfunction associated with vascular endothelial growth factor pathway inhibitors (VPIs) would seem to be the most plausible explanation for such events: it causes thromboembolic events and cardiovascular complications.

Experience of compounding total parenteral nutrition admixtures for preterm infants in a hospital pharmacy: evidence of calcium and phosphate compatibility problem.

OBJECTIVE: Parenterally fed preterm newborn infants require large amounts of calcium and phosphate in a low volume of solution. The lower the volume of solution, the higher is the possibility of precipitation of calcium hydrogen phosphate (CaHPO4). Precipitation could cause respiratory distress and pulmonary embolism, and the use of organic salts of calcium and phosphorus may reduce the likelihood of this problem. To date, no previous work on the stability of solutions with organic salts has been published in the literature. This study aims to evaluate the visible precipitation of calcium and phosphorus in total parenteral nutrition solutions. METHODS: 20 parenteral nutrition solutions were aseptically prepared in a laminar airflow hood in a clean room. The solutions are intended to facilitate precipitation, with the amino acid ratio below the standard concentration and other parameters also modulated to promote the precipitation of CaHPO4. The solutions contained dextrose, amino acids, calcium gluconate and fructose 1,6-bisphosphate. We did not use lipid emulsion so that we could see all precipitations. RESULTS: No visible precipitation was observed during 4 weeks of observation at 25°C. The only observed event was the change in colour of the solution, which became yellow, maybe because of a Maillard reaction. CONCLUSIONS: This study evaluated the compatibility of organic calcium and phosphorus in order to prevent the precipitation of CaHPO4 when preparing total parenteral nutrition solutions. The fact that no precipitation was observed is very significant as it indicates the compatibility of the ions, even though no instrumental analysis was performed.