Nicolau syndrome and localized panniculitis: a report of dual diagnoses with an emphasis on morphea profunda‐like changes following injection with glatiramer acetate

Abstract

Glatiramer acetate, given as a 40 mg subcutaneous injection thrice weekly, was recently approved by the FDA based on data suggesting better compliance and a more favorable side effect profile compared to lower dose, daily dosing. The most commonly reported adverse events are transient injection site reactions involving redness and pain at the site; however, more pronounced panniculitis and lipoatrophy have also been reported. Here, we present the case of a 51-year-old female treated with higher dose glatiramer acetate who presented with a cutaneous injection site reaction consistent with Nicolau syndrome. The excised specimen revealed typical glatiramer acetate-associated panniculitis, alongside subcutaneous sclerosis. This case shows the spectrum of cutaneous complications possible with glatiramer acetate injections, the finding of sclerosis being relatively infrequently reported. Given the relatively short duration of trials leading to FDA approval of thrice weekly dosing of glatiramer acetate, clinicians should perform careful clinical and histopathological evaluation and reporting of patients who experience injection site reactions.

Nicolau syndrome following subcutaneous glatiramer acetate injection

“…Nicolau syndrome is also known as livedoid dermatitis or embolism cutis medicamentosa and was first described as a rare cutaneous injection site reaction after intramuscular administration of bismuth. [ 1 ] It is a serious complication of injectable medications and characterized by severe pain, tenderness, and erythema. Lesions tend to progress rapidly to livedoid reticular, hemorrhagic patches, and subsequently to ulcers and skin necrosis.…”

“…After several weeks or months, the lesions heal by leaving atrophic scarring. [ 1 ] Although the reaction has been historically associated with bismuth, more recently, presentations with injectable forms of β-lactam antibiotics, nonsteroidal anti-inflammatory drugs, corticosteroids, lidocaine, and fillers such as hyaluronic acid have been reported. [ 1 ]…”

“…The most common side effects include transient mild localized skin reactions such as erythema, swelling, pain, irritation, and induration around the injection site. [ 1 2 ] Only a few cases of severe localized reactions known as Nicolau syndrome following glatiramer subacetate injection have been reported so far. [ 1 2 3 4 5 ]…”

A 65-Year-Old Male with a Large Plaque of Retiform Purpura with Impending Necrosis on the Right Lower Abdomen

“…2,3 In this report, the patient experienced NS after selfinjecting GA after approximately 8 years of prior GA therapy. There are other published reports of NS associated with GA, and reactions may occur years after starting GA. 1,2,4 The clinical presentation of NS is intense pain at the injection site immediately after administration, erythema and reticular or livedoid purpuric changes within a few hours, and necrotic ulceration within a few days that can progress into a scar in a few weeks. 1,4 The pathophysiology of NS likely involves ischemic damage from a thromboembolic occlusion or direct vascular injury that subsequently leads to occlusion.…”

“…1,3,4 NS is mainly attributed to improper injection technique and the risk of recurrence is low, so it is not a contraindication for continuing therapy. 1,4 NS may be avoided by using Z-track injections, long needles, auto-injectors, performing aspirations prior to injection, and injecting in regions with less blood vessels. 3 Our patient did not resume glatiramer therapy and four months later, his multiple sclerosis remained stable.…”