Abstract
Dear Editor:
Diclofenac is a nonsteroidal anti-inflammatory drug frequently prescribed as analgesic, anti-inflamatory, and antipyretic. 1 There are several well-known unwanted effects of diclofenac, among which skin necrosis is considered rare. 2
In many clinical situations, diclofenac's intramuscular (IM) administration is not possible, particularly in frail patients, because of cachexia and muscular atrophy. The subcutaneous (SC) administration of diclofenac has been reported as a safe and effective route in palliative care, 3 despite the potential for serious skin reactions to rarely occur. 4 We describe two patients who developed skin necrosis after diclofenac SC administration for the treatment of fever.
Case 1
A 72-year-old woman was totally dependent for all her activities of daily living. She was obese with multiple comorbidities—portal vein thrombosis, compression fracture of L1 vertebrae, total hip and right knee replacement surgery, and peptic ulcer disease.
Because her clinical condition had deteriorated suddenly, she was unable to take oral medication, and diclofenac 75 mg/3 ml SC was administered into her right thigh as an antipyretic to treat her fever. Thirty minutes after administration, an intensely dark purpuric patch of erythema 4 mm in diameter was observed at the injection site. The patient died a few hours after, so the natural course of this erythematous area could not be reviewed during her lifetime.
Case 2
An 88-year-old woman with Alzheimer's disease had previously had a right hip fracture and total hip replacement, and was living with hypertension, type 2 diabetes, and epilepsy. She developed a fever and prostration and was unable to take oral medication. Diclofenac 75 mg/3 ml SC was administered in her right thigh. Immediately after administration, an intense dark erythema with surface warmth appeared. Six hours later, the erythema darkened further, coalescing into a central lividoid violaceous patch, subsequently appearing to be slightly hemorrhagic. Two days later, a peripheral fluctuant margin appeared which contained pus (8 mm diameter). No drainage was performed, and daily local dressings were applied. The central patch evolved into necrotic tissue measuring 7 mm in diameter, and the surrounding erythema expanded a further 5 mm over one week of follow-up. Currently, the patch is detaching from healing skin using local dressings with an enzymatic debriding gel.
Discussion
Embolia cutis medicamentosa, also known as Nicolau Syndrome (NS), is a rare condition observed after IM injections or after SC injections have been inadvertently administered into muscle. 4 Its pathogenesis is uncertain, but the most common hypothesis suggests damage to an end subcutaneous artery.
In a paper about skin necrosis following injection of nonsteroidal anti-inflammatory medications, McGee and Davison stated that the two case reports of NS that they reviewed were almost certainly due to injections of NSAIDs subcutaneously rather than into muscle. This was also demonstrated by Cockshott et al. 5
Although the advisory information for diclofenac 75 mg/3 ml for injection mentions skin necrosis as a rare side effect after IM administration, it is not explicit about the potential harm from SC administration.
From personal communication with colleagues we postulate that there is little awareness about NS. These case reports may raise awareness of this potential unwanted effect within the professional and researcher community.