Nicolau`s syndrome T88.83

Freudenthal, 1924; Nicolau, 1925.

Embolia medicamentosa, also known as Nicolau syndrome, was first described after a bismuth injection in syphilis patients.

Rare, circumscribed (in the injection area), painful, dendritic, infarct-like, sharply defined zosteriform skin necroses after intramuscular, rarely after intra-articular or subcutaneous injections.

Intra-arterial, possibly para-arterial injection of drugs to be injected intramuscularly. Pathogenetically, the intra-arterial injection causes vasospasm and fibrinoid necrosis of arterioles and capillaries with thrombosis of the terminal tract. Potentially triggering drugs:

• Depotpenicillins
• Phenylbutazone-containing antirheumatic drugs
• Interferons
• Vaccines
• Glatiramer acetate (immunomodulator in MS).

Minutes to a few hours after i.m. injection. injection, painful, board-hard infiltration with livedo racemosa-like skin pattern (bizarre, tendril-like figures). Healing with hyperpigmentation. Central demarcation with formation of flat to sunken, hemorrhagic necroses possible after 24-72 hours. Rejection of the hemorrhagic scab. Development of deep ulcerations which heal with bizarrely shaped atrophic scars.

• Stage I: Edema extending beyond the injection area with inflammatory infiltration without necrosis.
• Stage II: Strong inflammatory reaction, macroscopically still no necrosis.
• Stage III: Necrosis of skin and/or muscles.
• Stage IV: Additional necrosis of pelvic organs.

Intravascular injections of filler materials are being reported with increasing frequency. In particular, injections into the dorsal nasal artery or the angular artery, if performed with sufficient pressure, can penetrate the supratrochlear or supraorbital arteries, reach the ophthalmic arteries and lead to hemorrhage (Mancha D et al. 2025).

Anti-inflammatory therapy with ibuprofen (e.g. Ibuprofen Stada, 2-3 times/day 200 mg p.o.). At the onset, vasodilators such as pentoxifylline (e.g. Trental 2 times/day 600 mg p.o.), nicotinic acid (Merz Spezial Dragees N 3 times/day 2-3 drg. p.o.) or papaverine derivatives such as moxaverine (e.g. Kollateral forte Drg., 2-3 times/day 1 drg. p.o.) can be tried.

Pain therapy with paracetamol (e.g. Ben-u-ron Tbl.) or possibly tramadol (e.g. Tramal Trp.).

If necessary, prophylactic systemic broad-spectrum antibiotics e.g. with ofloxacin (e.g. Tavanic) 2 times/day 100-200 mg p.o., in case of superinfection antibiotics according to antibiogram.

1. Beissert et al. (1999) Embolia cutis medicamentosa (Nicolau syndrome) after intra-articular injection. Dermatology 50: 214-216
2. Cherasse A et al. (2003) Nicolau's syndrome after local glucocorticoid injection. Joint Bone Spine 70: 390-392
3. Freudenthal W (1924) Local embolic bismogenol exanthema. Arch Dermatol Syph 147: 155-160
4. Littmann K, Albrecht KH, Richter HJ, Eigler FW (1984) Embolia cutis. Dtsch med Wschr 109: 800-805
5. Mancha D et al. (2025) Nicolau's syndrome: Treatment with hyperbaric oxygen therapy. J Dtsch Dermatol Ges 23:766-768.
6. Müller CSL et al. (2016) Diagnostic and histologic features of cutaneous vasculitides/vasculopathies. Act Dermatol 42: 286-301
7. Nicolau S (1925) Dermatite livédoide et gangreneuse de la fesse consécutive aux injections intramusculaires dans la syphilis. A propos d'un cas d'embolie artérielle bismuthique. Ann Mal Vén 20: 321-339