IFN injections, as well as subcutaneous injections of pain medication, allergy shots, and Depo-Provera, have also been reported to cause subcutaneous sarcoid-like granulomatous lesions. Surgical intervention is rarely required.
Treatment of Nicolau syndrome is conservative: dressing changes, debridement, bed rest, and pain control. Vitamin B 12 also produces localized sclerodermoid reactions. Biopsy of the IFN ISRs resembles lupus panniculitis. Patient education and autoinjectors can prevent this complication. IFN-β injections into subcutaneous tissue of the abdomen, buttocks, or thighs of patients with multiple sclerosis has resulted in similar lesions. It appears to be caused by periarterial injection leading to arterial thrombosis. There may be a particular risk with refrigerated medications that may contain crystals, which are meant to be warmed before injection. Nicolau syndrome has been seen with injection of many unrelated agents, including NSAIDs, local anesthetics, corticosteroids, antibiotics, IFN-α, sedatives, vaccines, and medroxyprogesterone acetate (Depo-Provera). The circulation of the limb may be affected, rarely leading to amputation. Muscle and liver enzymes may be elevated, and neurologic symptoms and sequelae occur in one third of patients. Eventually, over weeks to months, the ulcer heals with an atrophic scar. This becomes hemorrhagic, then ulcerates, often forming a deep ulcer many centimeters in diameter.
PLACEBO TINY BALLS PATCH
Within minutes to hours, the site develops an erythematous macule that evolves into a livedoid violaceous patch with dendrites.
PLACEBO TINY BALLS SKIN
Immediately after injection, local intense pain occurs and the overlying skin blanches (ischemic pallor). IM injections may produce a syndrome called embolia cutis medicamentosa, livedoid dermatitis, or Nicolau syndrome. These include chemotherapeutic agents (fluorouracil in particular, but multiple agents), calcium salts, radiocontrast material, and nafcillin. Pharmacologic agents that extravasate into tissue during IV infusion may cause local tissue necrosis, resulting from inherent tissue-toxic properties. These are of two typical forms: those associated with IV infusions and those related to intramuscular (IM) injections. In addition to allergic reactions, as described with vitamin K, cutaneous necrosis may occur at sites of medication injections. James MD, in Andrews' Diseases of the Skin, 2020 Injection Site Reactions
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