Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 7  |  Issue : 2  |  Page : 106-108  

A case of figurate urticaria by etanercept


1 Department of Experimental Medicine, Pharmacoepidemiology and Pharmacovigilance Centre of the Campania Region, Section of Pharmacology, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy
2 Department of Dermatology, Second University of Naples, Naples, Italy

Date of Submission04-Dec-2015
Date of Decision07-Jan-2016
Date of Acceptance26-Mar-2016
Date of Web Publication28-Jun-2016

Correspondence Address:
Maria Giuseppa Sullo
Department of Experimental Medicine, Pharmacoepidemiology and Pharmacovigilance Centre of the Campania Region, Section of Pharmacology, Second University of Naples, Via Costantinopoli 16, 80138 Naples
Italy
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.184777

Rights and Permissions
   Abstract 

Etanercept is a competitive inhibitor of tumor necrosis factor-alpha (TNF-α) a polypeptide hormone, involved in the development of the immune system, in host defense and immune surveillance. Even if the etanercept mechanism of action is not completely understood, it is supposed that it negatively modulates biological responses mediated by molecules (cytokines, adhesion molecules, or proteinases) induced or regulated by TNF. For this reason, it is widely used in the treatment of immunologicals diseases, such as rheumatoid and psoriatic arthritis, polyarticular juvenile idiopathic active, ankylosing spondylitis, and plaque psoriasis. Etanercept has a good tolerability profile. Adverse events related to skin are rare, arising usually in about 5% of patients treated with anti-TNF α. In this scenario, we describe a case of figurate urticaria arose after the re-administration of etanercept in a patient affected by psoriasis and hepatitis B. A 65-year-old man, affected by psoriasis, was hospitalized in September 2014 to the Regional Center for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The laboratory analysis detected positivity for hepatitis B virus (HBV) antigens. For this reason, it was administered to him lamivudine 100 mg/die about 30 days before to start etanercept treatment. The etanercept therapy has resulted in a progressive improving of skin manifestations, and the patient decided individually to stop the therapy. Afterwards, for worsening of the psoriatic lesions, he was again hospitalized and treated with the same therapeutic schedule (lamivudine followed by etanercept). Ten days after the start of therapy, the patient showed the onset of urticarial rash. Due to this, the treatment with lamivudine and etanercept was suspended and the patient's clinical conditions improved. It is probably that immunological disorders due to etanercept therapy and HBV infection could explain the onset of figurate urticaria in our patient. In this contest, the post-marketing surveillance confirms its important role in the monitoring of drugs tolerability and effectiveness.

Keywords: Adverse drug reaction, anti-tumor necrosis factor-alpha, urticaria figurate


How to cite this article:
Sessa M, Sullo MG, Mascolo A, Cimmaruta D, Romano F, Puca RV, Capuano A, Rossi F, Schiavo AL. A case of figurate urticaria by etanercept. J Pharmacol Pharmacother 2016;7:106-8

How to cite this URL:
Sessa M, Sullo MG, Mascolo A, Cimmaruta D, Romano F, Puca RV, Capuano A, Rossi F, Schiavo AL. A case of figurate urticaria by etanercept. J Pharmacol Pharmacother [serial online] 2016 [cited 2019 May 23];7:106-8. Available from: http://www.jpharmacol.com/text.asp?2016/7/2/106/184777


   Introduction Top


Etanercept is a competitive inhibitor of tumor necrosis factor (TNF) binding to cell surface TNF-Receptor, preventing TNF-mediated cellular responses by rendering TNF biologically inactive. Even though its mechanism of action is not completely known, it is supposed to modulate biologic responses controlled by additional downstream molecules (e.g., cytokines, adhesion molecules, or proteinases) that are induced or regulated by TNF. [1] TNF-α and lymphotoxin-alpha (LF-α), formerly known as TNF-β, are polypeptides hormones, members of the superfamily of TNF, composed of about 30 related molecules, encoded in the major histocompatibility complex Class III region. The TNF, mainly produced by monocytes/macrophages and activated T-cells, is involved in the development of the immune system, in host defense and immune surveillance. [2],[3],[4] Both TNF-α and LF-α share the same two monomeric receptors on the cell surface (p55 TNF receptor [TNFR] and p75 TNFR), part of the signal transduction system and both exist in soluble TNFR (sTNFR) forms produced by enzymatic cleavage induced by cell activation. [5],[6],[7],[8],[9] Etanercept is widely used in the treatment of rheumatoid arthritis in adults, psoriatic polyarticular juvenile idiopathic active in children and adolescents more than 2-year-old, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. [1] The Summary of Product Characteristics of etanercept include a long list of severe and non-severe adverse event. Infections due to immunosuppression, which was related to anti-TNF- α pharmacodynamics effects of etanercept. The skin-related adverse event usually arises in about 5% of patients treated with anti-TNF α. [10]

Regarding this, we reported an etanercept-induced figurate urticaria onset after re-administration of etanercept and lamivudine in a patient affected by psoriasis and hepatitis B virus (HBV) infection. The patient was followed with periodic follow-up at the Regional Centre for the treatment of psoriasis and Biological Drugs of the Second University of Naples.


   Case Report Top


A 65-year-old man, affected by psoriasis from the young age, was hospitalized in September 2014 to Regional Centre for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The patient denied the previous history of herbal medicines and drugs hypersensitivity. Laboratory result was positive for HBV antigens. Since other systemic drugs are contraindicated in this condition, a biological agent was preferred drug orienting clinicians to administer a biologic drug. [1] The patient started hepatitis B therapy with lamivudine tablets 100 mg/day. Hence, about 30 days after lamivudine administration, we began the treatment of psoriasis with etanercept 50 mg 2 fl by subcutaneous injection (s.c.)/week for 3 months, and then 1 fl s.c./week. Two medical examinations followed 30 and 90 days after first etanercept administration, showing a progressive resolution of cutaneous manifestations. For this reason, the patient decided on his own to stop the therapy. Afterward, for worsening of the psoriatic lesions, the patient was hospitalized again. During hospitalization, lamivudine was re-administered followed by etanercept after 30 days. Ten days after etanercept re-administration, the patient was hospitalized due to the onset of urticarial rash composed of lesion involving trunk and upper limbs. The lesions converged and assumed the character of figurate urticaria with well-delimited polycyclic pinkish contours, more marked at the periphery and itchy. Due to this, the treatment with lamivudine and etanercept was suspended, and the adverse event got better. The drug-adverse event association was postulated using Naranjo Probability Scale resulting possible (score of 4). [11]


   Discussion Top


Etanercept is a TNF blocker used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis. Apart from infections, the most common adverse events due to etanercept, severe skin reactions were also observed. Among these, in particular, erythematous skin lesions, multiform erythema localized to the trunk, legs, arms, shoulders, hands, and face were commonly observed. [1],[12],[13] Regarding multiforme erythema, a case-series reporting five cases of annular erythematous lesions was published in the literature in 2006. These types of adverse events were observed in patients treated with anti-TNF α, and particularly one of these patients was treated with etanercept. [12] In 2010, another case of multiform erythema raised 11 days after the first administration of adalimumab in a 67 years patient suffering from psoriasis and chronic infection by herpes simplex 2. The patient already presented the same adverse event during the previous treatment with etanercept. [13] According to literature, several etiopathogeneses could determine this condition, including allergic, infectious, neoplastic, autoimmune, and iatrogenic. [14] In our experience, we observed a case of figurative urticaria characterized by annular, ovular, and polycyclic shaped lesions with well-defined itchy margins that followed the administration of etanercept. Considering the potential role of drug-drug interactions in inducing adverse events in HBV patients, [15],[16] we assessed the interactions using the software Micromedex 2.0 (Truven Health Analytics, Inc. Greenwood Village, Colarodo). No drug-drug interactions were detected between lamivudine and etanercept. Therefore, we supposed a possible immunological mechanism to explain this adverse event. In particular, we cannot rule out the possibility that the previous exposure to etanercept-induced antidrug antibodies production from B-cell. [17] Antidrug antibody were commonly observed with biologic drugs, included anti-TNF. When a second etanercept administration was performed, these antibodies had to complement activation with immunocomplex deposition in dermis vessels, collagen damage, and consequently dermic vessels inflammation and onset of clinical manifestation. On the other hand, we cannot exclude the fact that positivity to HBV antigens could play a role in etiopathogeneses of this case of figurate urticaria. Several authors described the role of deposition of circulating immune complexes anti-HBV antigens in the pathogenesis of HBV-related urticaria. Skin lesions related to HBV could be considered as a prodromal sign of acute hepatitis B infection. For this type of reactions immune-mediated mechanism have been supposed to this kind of clinical manifestations. HBV-related hepatic complications may be associated with extrahepatic manifestations such as urticaria skin lesion. [13],[18] Our case contributes to the current body of literature on this topic, mainly characterized by cases obtained from post-marketing surveillance. Post-marketing surveillance represents the cornerstone of pharmacovigilance especially for those adverse event, which are rare, to obtain additional information potentially useful to better understand the safety profile of the drugs in a real life contest. [19],[20],[21],[22],[23],[24],[25],[26],[27],[28]


   Conclusion Top


We described a case of figurate urticaria arose after the re-administration of etanercept inpatient HBV positive. It is probably that immunological disorders due to etanercept therapy and HBV infection could explain the onset of figurate urticaria in our patient. In this scenario, the post-marketing surveillance confirms its important role in the monitoring of drugs tolerability and effectiveness, especially for drugs such as anti TNF-α, whose safety profile is not yet fully known.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Summary of Product Characteristics - Enbrel 25 mg Powder and Solvent for Injectable Solution. Available from: https://www.farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_001533_034675_RCP.pdf&retry=0&sys=m0b1l3. [Last accessed on 2015 Nov 11].  Back to cited text no. 1
    
2.
Aggarwal BB, Natarajan K. Tumor necrosis factors: Developments during the last decade. Eur Cytokine Netw 1996;7:93-124.  Back to cited text no. 2
    
3.
Dinarello CA, Moldawer LL. Proinflammatory and Anti-inflammatory Cytokines in Rheumatoid Arthritis: A Primer for Clinicians. 3 rd ed. Thousand Oaks: Amgen; 2001.  Back to cited text no. 3
    
4.
Ruddle NH. Lymphoid neo-organogenesis: Lymphotoxin′s role in inflammation and development. Immunol Res 1999;19:119-25.  Back to cited text no. 4
    
5.
Smith CA, Davis T, Anderson D, Solam L, Beckmann MP, Jerzy R, et al. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 1990;248:1019-23.  Back to cited text no. 5
    
6.
Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CW, Bitzan P, et al. Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum 2000;43:2501-12.  Back to cited text no. 6
    
7.
Darnay BG, Aggarwal BB. Signal transduction by tumour necrosis factor and tumour necrosis factor related ligands and their receptors. Ann Rheum Dis 1999;58 Suppl 1:I2-I13.  Back to cited text no. 7
    
8.
Which X, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng W, et al. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest 2002;110:515-26.  Back to cited text no. 8
    
9.
Higuchi M, Aggarwal BB. TNF induces internalization of the p60 receptor and shedding of the p80 receptor. J Immunol 1994;152:3550-8.  Back to cited text no. 9
    
10.
Galaria NA, Werth VP, Schumacher HR. Leukocytoclastic vasculitis due to etanercept. J Rheumatol 2000;27:2041-4.  Back to cited text no. 10
    
11.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 11
[PUBMED]    
12.
Deng A, Harvey V, Sina B, Strobel D, Badros A, Junkins-Hopkins JM, et al. Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors. Arch Dermatol 2006;142:198-202.  Back to cited text no. 12
    
13.
Ahdout J, Haley JC, Chiu MW. Erythema multiforme during anti-tumor necrosis factor treatment for plaque psoriasis. J Am Acad Dermatol 2010;62:874-9.  Back to cited text no. 13
    
14.
Toledo-Alberola F, Betlloch-Mas I. Erythema ranges we make of infancy. Actas Dermosifiliogr 2010;101:473-84.  Back to cited text no. 14
    
15.
Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci 2013;18:601-10.  Back to cited text no. 15
    
16.
Caroleo B, Staltari O, Gallelli L, Perticone F. Reactivation of chronic hepatitis B during treatment with tenofovir disoproxil fumarate: Drug interactions or low adherence? BMJ Case Rep 2015;2015. pii: Bcr2015209586.  Back to cited text no. 16
    
17.
Vincent FB, Morand EF, Murphy K, Mackay F, Mariette X, Marcelli C. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: A real issue, a clinical perspective. Ann Rheum Dis 2013;72:165-78.  Back to cited text no. 17
    
18.
Toledo-Alberola F, Betlloch-Mas I. Annular erythema of infancy. Actas Dermosifiliogr 2010;101:473-84.  Back to cited text no. 18
    
19.
Mazzitello C, Esposito S, De Francesco AE, Capuano A, Russo E, De Sarro G. Pharmacovigilance in Italy: An overview. J Pharmacol Pharmacother 2013;4 Suppl 1:S20-8.  Back to cited text no. 19
    
20.
Ruggiero S, Rafaniello C, Bravaccio C, Grimaldi G, Granato R, Pascotto A, et al. Safety of attention-deficit/hyperactivity disorder medications in children: An intensive pharmacosurveillance monitoring study. J Child Adolesc Psychopharmacol 2012;22:415-22.  Back to cited text no. 20
    
21.
Rafaniello C, Ianniello B, De Vizia M, Mercogliano A, Lettieri B, Rinaldi B, et al. Cardiorespiratory effects of change in posture after spinal anesthesia with hyperbaric bupivacaine. Minerva Med 2011;102:501-4.  Back to cited text no. 21
    
22.
Capuano A, Irpino A, Gallo M, Ferrante L, Illiano ML, Rinaldi B, et al. Regional surveillance of emergency-department visits for outpatient adverse drug events. Eur J Clin Pharmacol 2009;65:721-8.  Back to cited text no. 22
    
23.
Capuano A, Motola G, Russo F, Avolio A, Filippelli A, Rossi F, et al. Adverse drug events in two emergency departments in Naples, Italy: An observational study. Pharmacol Res 2004;50:631-6.  Back to cited text no. 23
    
24.
Mumoli L, Gambardella A, Labate A, Succurro E, De Sarro G, Arturi F, et al. Rosacea-like facial rash related to metformin administration in a young woman. BMC Pharmacol Toxicol 2014;15:3.  Back to cited text no. 24
    
25.
Calderazzo M, Rende P, Gambardella P, De Sarro G, Gallelli L. A case of interstitial lung disease probably related to rituximab treatment. Drug Saf Case Rep 2015;2:8.  Back to cited text no. 25
    
26.
Giofrè C, Scicchitano F, Palleria C, Mazzitello C, Ciriaco M, Gallelli L, et al. Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis. J Pharmacol Pharmacother 2013;4 Suppl 1:S55-60.  Back to cited text no. 26
    
27.
Scicchitano F, Giofrè C, Palleria C, Mazzitello C, Ciriaco M, Gallelli L, et al. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis. J Res Med Sci 2012;17:872-5.  Back to cited text no. 27
[PUBMED]  Medknow Journal  
28.
Rende P, Paletta L, Gallelli G, Raffaele G, Natale V, Brissa N, et al. Retrospective evaluation of adverse drug reactions induced by antihypertensive treatment. J Pharmacol Pharmacother 2013;4 Suppl 1:S47-50.  Back to cited text no. 28
    



This article has been cited by
1 Adverse drug reactions during hepatitis C treatment with direct-acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting syste
Maurizio Sessa,Francesca Futura Bernardi,Andrea Vitale,Beniamino Schiavone,Giulia Gritti,Annamaria Mascolo,Michele Bertini,Cristina Scavone,Liberata Sportiello,Francesco Rossi,Annalisa Capuano
Journal of Clinical Pharmacy and Therapeutics. 2018;
[Pubmed] | [DOI]
2 Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system?
Maurizio Sessa,Concetta Rafaniello,Cristina Scavone,Annamaria Mascolo,Gabriella di Mauro,Annamaria Fucile,Francesco Rossi,Liberata Sportiello,Annalisa Capuano
Expert Opinion on Drug Safety. 2018; : 1
[Pubmed] | [DOI]
3 Pillars and Pitfalls of the New Pharmacovigilance Legislation: Consequences for the Identification of Adverse Drug Reactions Deriving From Abuse, Misuse, Overdose, Occupational Exposure, and Medication Errors
Maurizio Sessa,Gabriella di Mauro,Annamaria Mascolo,Concetta Rafaniello,Liberata Sportiello,Cristina Scavone,Annalisa Capuano
Frontiers in Pharmacology. 2018; 9
[Pubmed] | [DOI]
4 Can causality assessment fulfill the new European definition of adverse drug reaction? A review of methods used in spontaneous reporting
Annamaria Mascolo,Cristina Scavone,Maurizio Sessa,Gabriella di Mauro,Daniela Cimmaruta,Valentina Orlando,Francesco Rossi,Liberata Sportiello,Annalisa Capuano
Pharmacological Research. 2017; 123: 122
[Pubmed] | [DOI]
5 Campania Preventability Assessment Committee (Italy): A Focus on the Preventability of Non-steroidal Anti-inflammatory Drugsć Adverse Drug Reactions
Maurizio Sessa,Liberata Sportiello,Annamaria Mascolo,Cristina Scavone,Silvia Gallipoli,Gabriella di Mauro,Daniela Cimmaruta,Concetta Rafaniello,Annalisa Capuano
Frontiers in Pharmacology. 2017; 8
[Pubmed] | [DOI]
6 Etanercept
Reactions Weekly. 2016; 1614(1): 78
[Pubmed] | [DOI]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References

 Article Access Statistics
    Viewed1438    
    Printed29    
    Emailed0    
    PDF Downloaded328    
    Comments [Add]    
    Cited by others 6    

Recommend this journal