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Nicolau's syndrome in a newborn caused by triple DTP (diphtheria-tetanus-pertussis) vaccination

2006; Elsevier BV; Volume: 54; Issue: 5 Linguagem: Inglês

10.1016/j.jaad.2005.09.046

1097-6787

Emel Erkek, Fatma Tunçez, Cihat Şanlı, Deniz Duman, Gülcan Saylam Kurtipek, Yeter Bağci, Ergin Ayaşlıoğlu,

Heparin-Induced Thrombocytopenia and Thrombosis

To the Editor: Nicolau's syndrome (NS), or embolia cutis medicamentosa, is a rare cutaneous reaction to intramuscular injection of certain drugs. It is characterized by livedoid patches of aseptic necrosis involving the skin, subcutaneous tissue, and even muscle at the injection site.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar, 3Reding E.L. Poletti E.E. Postinjection painful eruption: self-assessment examination of the American Academy of Dermatology.J Am Acad Dermatol. 2003; 48: 472-473Google Scholar Historically, the usual scenario was intramuscular injection of bismuth salts used for the treatment of syphilis.2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar Currently, sporadic cases of NS are still being encountered. A 3-month-old baby was referred to the department of dermatology with a 1-week history of painful swelling on his right thigh. His mother described immediate redness and swelling at the injection site of a diphtheria-tetanus-pertussis (DPT) vaccine. Within the following week, redness and swelling had become intense and slight central depression had developed. The baby cried when the affected area was touched. Dermatologic examination revealed a circumscribed, irregular, edematous, red-violet, 4-cm plaque located on the right thigh. Skin lines were prominent over the plaque (Fig 1). The lesion was tender on light touch as evidenced by the baby's restlessness. A topical steroid cream and EMLA (an eutectic mixture of local anesthetics) were prescribed. Typical livedoid necrosis was observed within 1 week and an atrophic scar remained at the site of injection at a 2-month follow-up (Fig 2).Fig 2Atrophic scar at site of DPT injection at 2-month follow-up.View Large Image Figure ViewerDownload (PPT) The pathogenesis of NS is obscure. Intra-arterial or periarterial injection of the offending medication is suspected as the most plausible explanation for this abnormal cutaneous reaction.3Reding E.L. Poletti E.E. Postinjection painful eruption: self-assessment examination of the American Academy of Dermatology.J Am Acad Dermatol. 2003; 48: 472-473Google Scholar, 4Ezzedine K. Vadoud-Seyedi J. Heenen M. Nicolau syndrome following diclofenac administration.Br J Dermatol. 2004; 150: 385-387Crossref PubMed Scopus (45) Google Scholar The mechanism may involve direct trauma or arterial embolism caused by drug or compression of an artery after a paravasal injection.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 4Ezzedine K. Vadoud-Seyedi J. Heenen M. Nicolau syndrome following diclofenac administration.Br J Dermatol. 2004; 150: 385-387Crossref PubMed Scopus (45) Google Scholar, 5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar Another hypothesis suggests a vascular pathogenesis (ie, arterial vasospasm may follow penetration of drug microcrystals into a blood vessel).4Ezzedine K. Vadoud-Seyedi J. Heenen M. Nicolau syndrome following diclofenac administration.Br J Dermatol. 2004; 150: 385-387Crossref PubMed Scopus (45) Google Scholar Injection of the offending medication immediately leads to severe pain at the injection site as a result of involvement of peripheral sensory nerves. Immediate pallor and edema develop, followed by a circumscribed red-violet, hemorrhagic plaque with dendritic extensions. Necrotic plaques, ulcers, bullae, erosions, and crusts may be observed over the livedoid plaque.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar, 5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar The lesion gradually heals within a few months and an atrophic scar remains at site of injection.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar Although the gluteal region is the most common site for NS,5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar other sites of injection may also be involved. A potential site in pediatric patients is the thigh, which was the location in our case. Skin biopsy in the acute phase of NS reveals necrosis of the epidermis and thrombosis of small and medium blood vessels. Conservative treatment with dressings, debridement, and pain control are the mainstay of therapy.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar Topical steroids may be worth trying.5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar Surgical intervention is rarely required.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar, 5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar In our case a topical steroid cream and EMLA were effective in alleviation of pain and reduction of erythema and swelling. However, one must be cautious about overuse of EMLA cream in an infant. The list of medications associated with NS includes bismuth, pyrazolone derivatives (phenylbutazone), diclofenac, ibuprofen, vitamin B complex, sulfapyridine, tetracycline, streptomycin, sulfonamide, lidocaine, phenobarbital, chlorpromazine, dexamethasone, triamcinolone, vitamin K, diphenhydramine, interferon alfa, gentamicin, and ketoprofen.1Lee M.W. Kim K.J. Choi J.H. Sung K.J. Moon K.C. Koh J.K. A case of embolia cutis medicamentosa.J Dermatol. 2003; 30: 927-928PubMed Google Scholar, 2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar, 3Reding E.L. Poletti E.E. Postinjection painful eruption: self-assessment examination of the American Academy of Dermatology.J Am Acad Dermatol. 2003; 48: 472-473Google Scholar, 4Ezzedine K. Vadoud-Seyedi J. Heenen M. Nicolau syndrome following diclofenac administration.Br J Dermatol. 2004; 150: 385-387Crossref PubMed Scopus (45) Google Scholar, 5Kohler L.D. Schwedler S. Worret W.I. Embolia cutis medicamentosa.Int J Dermatol. 1997; 36: 197Crossref PubMed Scopus (30) Google Scholar, 6Nagore E. Torrelo A. Gonzalez-Mediero I. Zambrano A. Livedoid skin necrosis (Nicolau syndrome) due to triple vaccine (DTP) injection.Br J Dermatol. 1997; 137: 1030-1031Crossref PubMed Scopus (40) Google Scholar Cases of NS due to intramuscular antiflu and triple DPT vaccinations have also been described.2Corazza M. Capozzi O. Virgilit A. Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts and various other non-steroidal anti-inflammatory drugs.J Eur Acad Dermatol Venereol. 2001; 15: 585-588Crossref PubMed Scopus (63) Google Scholar, 6Nagore E. Torrelo A. Gonzalez-Mediero I. Zambrano A. Livedoid skin necrosis (Nicolau syndrome) due to triple vaccine (DTP) injection.Br J Dermatol. 1997; 137: 1030-1031Crossref PubMed Scopus (40) Google Scholar Vaccination may be a factor preceding the development of NS in pediatric patients and triple DPT vaccine should be considered as an offending medication in neonatal or childhood NS.