CASE REPORT Nicolau syndrome after lumbar puncture: A case report in a 22-month-old girl Kristina Navrazhina, BA, Brienne D Cressey, MD, MBA, and Horatio F Wildman, MD New York, New York Key words: embolia cutis medicamentosa; lumbar puncture; necrosis; Nicolau syndrome INTRODUCTION Nicolau syndrome (NS) is a rare, aseptic cutaneous necrosis that may involve the subcutaneous and muscle tissue layers.1 This syndrome is associated with intramuscular, subcutaneous, intravenous, and intra-articular injections of antibiotics, local anesthetics, glucocorticoids, nonsteroidal antiinflammatory drugs, hyaluronic acid, vaccinations, and vitamins.2-5 NS presents as an immediate and severe pain at the injection site and a clearly demarcated livedolike discoloration of the skin that progresses to cutaneous necrosis with potential involvement of the underlying tissues.2,3 Although the pathophysiology of NS is debated, multiple theories implicate occlusion of cutaneous vessels after iatrogenic insult as an inciting cause.1,2 Here, we present the first case, to our knowledge, of NS caused by lumbar puncture CASE REPORT Abbreviation used: NS: Nicolau syndrome Fig Retiform purpuric patch on the lumbosacral area occurring day after lumbar puncture A 22-month-old girl with a medical history of failure to thrive presented to an outside hospital with fever and a single tonic-clonic seizure She had prerenal acute renal insufficiency, transaminitis, and anemia Workup included lumbar puncture with local lidocaine injection without difficulty She was transferred to our tertiary medical center for further treatment The dermatology department was consulted for a new-onset retiform purpuric patch on the lumbosacral area that developed day after the lumbar puncture (Fig 1) A workup, including biopsy and tissue culture, was performed to rule out other causes of large plaque retiform purpura, such as calciphylaxis, warfarin necrosis, and heparininduced thrombocytopenia syndrome Laboratory data were significant for creatinine level of 2.76, aspartate aminotransferase level of 293, alanine aminotransferase level of 111, hemoglobin value of 6.4, and hematocrit value of 19.3 Values for platelet count, coagulation studies, antiphospholipid panel, protein C and S, and antineutrophil cytoplasmic antibodies were within normal limits The tissue culture had no growth Histopathology found pauci-inflammatory thrombogenic vasculopathy affecting capillaries and venules throughout the dermis and subcutaneous fat with endothelial necrosis and sloughing into vascular lumens (Fig 2) Concomitant acrosyringeal, straight eccrine duct, and eccrine coil necrosis was observed A pathologic diagnosis of NS was made The affected From the Department of Dermatology, Weill Cornell Medical College Funding sources: None Conflicts of interest: None declared Drs Cressey and Wildman presented this report at the American Academy of Dermatology, Gross & Microscopic Symposium, 74thAnnual Meeting, Washington, DC, March 2016 Correspondence to: Horatio F Wildman, MD, Department of Dermatology, Weill Cornell Medical College, 1305 York Avenue 9th Floor, New York, NY 10021 E-mail: hfw2001@ med.cornell.edu JAAD Case Reports 2017;3:33-5 2352-5126 Ó 2017 by the American Academy of Dermatology, Inc Published by Elsevier, Inc This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/) http://dx.doi.org/10.1016/j.jdcr.2016.09.004 33 34 Navrazhina, Cressey, and Wildman JAAD CASE REPORTS JANUARY 2017 Fig A, Hematoxylin-eosin stain shows pauci-inflammatory thrombotic vasculopathy involving the capillaries and venules with concomitant ischemic necrosis of the epidermis B, Deposits of C5b-9 within the microvasculature are seen using a diaminobenzidine technique on paraffin-embedded, formalin-fixed tissue, indicative of vascular complement activation Fig Necrosis of the retiform plaque observed week after presentation site was treated with mupirocin ointment followed by white petrolatum impregnated gauze and nonadhesive dressings (Fig 3) Necrotic areas were debrided and required split-thickness grafting The cause of the patient’s transaminitis and anemia was attributed to acute Epstein-Barr virus infection, supported by a positive Epstein-Barr virus polymerase chain reaction result After month, the wound on the lumbosacral area healed well with mild hypertrophy DISCUSSION NS, also known as embolia cutis medicamentosa and livedolike dermatitis, is a rare ischemic necrosis of the skin that may extend into the underlying muscular tissue.6 NS presents as an area of immediate, intense pain and pallor with development of a well-defined, livedolike violaceous patch that eventually undergoes hemorrhagic transformation and subsequent necrosis.1,7 The ensuing eschar sloughs off to reveal an ulcer that heals over several months, resulting in an atrophic scar or pigmentation.1,3,6 Tissue damage secondary to NS can lead to extensive skin and muscle tissue loss, potentially resulting in hypoesthesia, nerve damage, and paraplegia.2,6 Treatment remains controversial and is contingent on the extent of the necrosis.1 Conservative methods include dressing changes and analgesics, whereas surgical debridement and partial-thickness skin grafts may be required in more complicated cases.1,7 Immediate treatment focuses on mitigating vessel occlusion and includes using heparin as a thrombolytic agent, pentoxiphylline to decrease blood viscosity, and hyperbaric oxygen to increase oxygen extraction.3,4 In more severe cases, surgical debridement can reduce the risk of infection and improve wound healing.4 Imaging, including computerized tomography scans and magnetic resonance imaging, can be useful to define the extent of tissue involvement.1 NS was first reported in 1925 after the introduction of intramuscular injections of bismuth salt as the treatment of syphilis.6,7 To date, NS has been associated with intramuscular (nonsteroidal antiinflammatory drugs, vaccinations, bismuth, hydroxyzine, penicillins), intra-articular (glucocorticoids), subcutaneous (pegylated interferon-a, lidocaine 1%), intravenous (polidocanol 1%), and subacromial (triamcinolone acetate) injections.1,4 Possibly because of the high prevalence of intramuscular injections in the pediatric population, children are at higher risk for NS.8 However, NS in the pediatric population remains a rare phenomenon,3 with reported cases occurring after intramuscular vitamin K injection or diphtheria, tetanus, and pertussis vaccine administration.8,9 To date, no studies address NS across different patient demographics JAAD CASE REPORTS VOLUME 3, NUMBER Although the precise pathogenesis of NS remains unclear, several predominant hypotheses have emerged based on histologic examination.3 One theory suggests that inflammation caused by perivascular injection of a substance causes injury to cutaneous arteries and subsequent necrosis of the skin Another hypothesis suggests that periarterial or perineural injection causes severe localized pain that triggers overactivation of the sympathetic system, leading to vasospasm and circulation compromise A third hypothesis entails intra-arterial injection of crystalloid drugs inducing an embolic occlusion of cutaneous arteries, resulting in tissue necrosis.2,3 As has been shown previously, that C5b-9 deposition is involved with vascular injury in another vasculopathy, the presence of C5b-9 microvascular deposits in our case may suggest that vascular complement activation results in Cb5-9 microvascular deposition, thrombosis, and subsequent tissue injury.10 To our knowledge, this case is the first reported case of NS after lumbar puncture The low incidence and unclear pathophysiology make prevention of NS challenging It has been previously reported that subcutaneous injection of 1% lidocaine before breast core needle biopsy caused NS in an adult woman.1 Local lidocaine injection in our case may have played an inciting role in the microvascular injury Given prevailing theories suggesting that NS occurs secondary to a local insult, physicians performing lumbar punctures should be cognizant of technical aspects of the procedure that increase the likelihood of damage to cutaneous vasculature These aspects include, but are not limited to, requiring multiple attempts, having difficulty entering the subarachnoid space, or requiring multiple lidocaine injections The most common differential diagnosis for cutaneous complications after lumbar puncture includes hematoma and active bleeding Nonetheless, Navrazhina, Cressey, and Wildman 35 when immediate severe pain and subsequent characteristic livedolike rash and tissue necrosis are observed at the procedural site after lumbar puncture, clinicians should maintain a high suspicion for NS The authors thank Dr Cynthia Magro, Professor of Pathology and Laboratory Medicine at NewYorkPresbyterian Hospital/Weill Cornell Medical Center for establishing the pathologic diagnosis in this case and providing the images for this case report REFERENCES Garcıa-Vilanova-Comas A, Fuster-diana C, Cubells-Parrilla M, Perez-Ferriols MD, Perez-Valles A, Roig-Vila JV Nicolau syndrome after lidocaine injection and cold application: a rare complication of breast core needle biopsy Int J Dermatol 2011;50(1):78-80 Enshaei A, Afshar A Compartment Syndrome of the Calf Due to Nicolau Syndrome Arch Bone Jt Surg 2016;4(1):87-89 McKinney C, Sharma N, Jerath RS Livedoid dermatitis (Nicolau syndrome) following intra-articular glucocorticoid injection J Clin Rheumatol 2014;20(6):339-340 Nischal K, Basavaraj H, Swaroop M, Agrawal D, Sathyanarayana B, Umashankar N Nicolau syndrome: an iatrogenic cutaneous necrosis J Cutan Aesthet Surg 2009; 2(2):92-95 Andre P, Haneke E Nicolau syndrome due to hyaluronic acid injections J Cosmet Laser Ther 2016;18(4):239-244 Kim SK, Kim TH, Lee KC Nicolau syndrome after intramuscular injection: cases Arch Plast Surg 2012;39(3):249-252 Bozkaya TA, Demirel G, Ormeci T, et al Anticoagulant and vasodilator therapy for Nicolau syndrome following intramuscular benzathine penicillin injection in a year old boy Arch Argent Pediatr 2016;114(3):e184-e186 Puvabanditsin S, Garrow E, Weerasethsiri R, Joshi M, Brandsma E Nicolau’s syndrome induced by intramuscular vitamin K injection in two extremely low birth weight infants Int J Dermatol 2010;49(9):1047-1049 Nagore E, Torrelo A, Gonzalez-Mediero I, Zambrano A Livedoid skin necrosis (Nicolau syndrome) due to triple vaccine (DTP) injection Br J Dermatol 1997;137(6):1030-1031 10 Magro CM, Poe JC, Kim C, et al Degos disease: a C5b-9/ interferon-a-mediated endotheliopathy syndrome Am J Clin Pathol 2011;135(4):599-610 ...34 Navrazhina, Cressey, and Wildman JAAD CASE REPORTS JANUARY 2017 Fig A, Hematoxylin-eosin stain shows pauci-inflammatory thrombotic vasculopathy involving the capillaries and venules... Bozkaya TA, Demirel G, Ormeci T, et al Anticoagulant and vasodilator therapy for Nicolau syndrome following intramuscular benzathine penicillin injection in a year old boy Arch Argent Pediatr... Rheumatol 2014;20(6):339-340 Nischal K, Basavaraj H, Swaroop M, Agrawal D, Sathyanarayana B, Umashankar N Nicolau syndrome: an iatrogenic cutaneous necrosis J Cutan Aesthet Surg 2009; 2(2):92-95 Andre