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Case Report

Case Report: Nicolau syndrome due to etofenamate injection

[version 1; peer review: 2 approved]
PUBLISHED 12 Jun 2017
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Abstract

Nicolau syndrome, also known as embolia cutis medicomentosa, is a rare complication characterized by tissue necrosis that occurs after injection of drugs. The exact pathogenesis is uncertain, but there are several hypotheses, including direct damage to the end artery and cytotoxic effects of the drug. Severe pain in the immediate postinjection period and purplish discoloration of the skin with reticulate pigmentary pattern is characteristic of this syndrome. Diagnosis is mainly clinical and there is no standard treatment for the disease. Etofenamate is a non-steroidal anti-inflammatory drug and a non-selective cyclooxygenase inhibitor. Cutaneous adverse findings caused by etofenamate are uncommon. Herein, we present a case with diagnosis of Nicolau syndrome due to etofenamate injection, which is a rare occurrence.

Keywords

Complication, etofenamate, Nicolau syndrome

Introduction

Nicolau syndrome is a rare complication caused by intramuscular injection of various medications1. The necrosis in the injection site of skin and sometimes muscle is a characteristic feature of this syndrome1. The development of acute vasospasm following intravenous or around the vein injection is the most widely accepted hypothesis in its pathogenesis1. Etofenamate is an anti-inflammatory drug that non-selectively inhibits the cyclooxygenase (COX) pathway2. Herein, we present a rare case of Nicolau syndrome after etofenamate injection.

Case report

An 81-year-old woman was admitted to our clinic with a painful necrotic ulcer in the left gluteal region. Her medical history, which was non-specific, except for back pain, revealed an intramuscular etofenamate injection (1000 mg), due to back pain, 15 days before. Dermatological examination revealed a painful ulcerous plaque with a black necrotic crest in the lateral part of the left gluteal region. This ulcerous plaque appeared indurated and erythematous in its surrounding (Figure 1). Her complaints started with erythematous swelling and pain in the injection site approximately ten days ago. Subsequently, the ulcer developed in the lesion area of the patient's erythematous swelling. There were not any abnormal parameters in both complete blood count and routine biochemistry tests. The patient was diagnosed with Nicolau syndrome based on her medical history and clinical signs and symptoms. Biopsy from the lesion area was not obtained, as it could develop more necrosis in the lesion. Etofenamate treatment was discontinued.

0ddb9531-6984-4c2c-b2f0-a77c57ba3ff9_figure1.gif

Figure 1. Black, necrotic ulcerated plaque on the gluteal region 15 days following etofenamate injection.

Local wound care with saline solution once a day and topical 2% mupirocin twice a day was applied to the lesion and the patient was referred to the Department of Plastic Surgery for the debridement of the necrotic tissue. After surgical debridement by the plastic surgeon, and continuation of local wound care (as above), the ulcer lesion was completely regressed, leaving an atrophic scar after one month (Figure 2).

0ddb9531-6984-4c2c-b2f0-a77c57ba3ff9_figure2.gif

Figure 2. Large atrophic, deppressed scar on the gluteal region one month following treament.

Discussion

Nicolau syndrome, also known as embolia cutis medicamentosa, is defined as an iatrogenic syndrome following intramuscular injections. However, cases with Nicolau syndrome after subcutaneous, intravenous, or intraarticular injection have been recently reported in the literature35.

Although the pathogenesis of Nicolau syndrome is not fully understood, direct vascular damage, perivascular inflammation, and vascular contraction following an injection are thought to be responsible6. In addition, it has been suggested that pharmacological properties of an individual drug may play a role in the pathogenesis6.

Etofenamate is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic, and anti-inflammatory effects. It inhibits the COX pathway and blocks prostaglandin synthesis non-selectively2. It has been shown that NSAIDs play a key role in the pathogenesis of vascular spasm induction and local circulation blockage, inhibiting the COX enzyme and prostaglandin synthesis7. In addition, these drugs have a central role in inducing vascular spasm and blocking local circulation, inhibiting the COX enzyme and prostaglandin synthesis in the pathogenesis of this syndrome7.

In Nicolau syndrome, following the injection of the clinically active agent, erythematous, ecchymosed, and reticular lesions appear in the injection site with severe pain. Progressive ischemic necrosis with sharp edges in a livedoid pattern develops later. Lesions often heal leaving atrophic scars8.

Nicolau syndrome has no definitive treatment. In the early period, the main goal of therapy is to prevent the development of necrosis. Therefore, pentoxifylline, hyperbaric oxygen, intravenous alprostadil, and heparin, which strengthen the vasculature, can be used4. Intralesional steroid injection can also be effective by reducing inflammation. Surgical debridement should be performed in the case of necrosis4. Systemic antibiotics should be used in case of secondary infection4. Contraction and deformity development are among late complications, and surgical treatment can be required in these cases9. Nicolau syndrome is uncommon with proper injection techniques - aspirating just before injecting medication has been suggested as a technique of preventing this syndrome10.

Conclusion

As a result, applications of standard drug injection rules are essential in prevention from Nicolau syndrome. It should be kept in mind that Nicolau syndrome could also develop following the use of intramuscular etofenamate.

Consent

Written informed consent was obtained from the patient for the publication of the patient’s clinical details and accompanying images.

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Ozlu E, Baykan A, Ertas R et al. Case Report: Nicolau syndrome due to etofenamate injection [version 1; peer review: 2 approved]. F1000Research 2017, 6:867 (https://doi.org/10.12688/f1000research.11705.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 12 Jun 2017
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Reviewer Report 14 Aug 2017
Burak Tekin, Private dermatology specialist, Istanbul, Turkey 
Approved
VIEWS 6
Well-presented case of Nicolau syndrome.
Dermatologists seem to be familiar with this entity, however, all healthcare workers may encounter this reaction in their clinical practice since injectable NSAIDs are commonly used. This report may serve the purpose of increasing ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Tekin B. Reviewer Report For: Case Report: Nicolau syndrome due to etofenamate injection [version 1; peer review: 2 approved]. F1000Research 2017, 6:867 (https://doi.org/10.5256/f1000research.12646.r24881)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Views
10
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Reviewer Report 03 Jul 2017
Mahmut Sami Metin, Department of Dermatology, Faculty of Medicine, Atatürk University, Erzurum, Turkey 
Approved
VIEWS 10
  • The article has been well designed.
  • Pictures are good.
  • Discussion is
... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Metin MS. Reviewer Report For: Case Report: Nicolau syndrome due to etofenamate injection [version 1; peer review: 2 approved]. F1000Research 2017, 6:867 (https://doi.org/10.5256/f1000research.12646.r23434)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 12 Jun 2017
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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