Accepted Manuscript Cutaneous Vasculitis secondary to Anti-TNF therapy A case report Dr Uday N. Shivaji, Dr Ashish Kumar Awasthi, Dr Rebecca Aherne
PII: DOI: Reference:
S1542-3565(15)00666-7 10.1016/j.cgh.2015.05.012 YJCGH 54293
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 8 May 2015 Please cite this article as: Shivaji UN, Awasthi AK, Aherne R, Cutaneous Vasculitis secondary to Anti-TNF therapy A case report, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/ j.cgh.2015.05.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
Cutaneous Vasculitis
RI PT
ACCEPTED MANUSCRIPT
TE D
M AN U
SC
Cutaneous Vasculitis secondary to Anti-TNF therapy A case report
Submission of manuscript by:
AC C
EP
Dr.Uday N Shivaji (Corresponding author) Specialty Registrar in Gastroenterology Walsall Manor Hospital, UK Mob-00447908587589 Email- [email protected] Concept, reporting, writing and final approval
Dr.Ashish Kumar Awasthi Consultant Gastroenterologist Walsall Manor Hospital, UK Concept, critical revision and final approval Dr.Rebecca Aherne House Officer Walsall Manor Hospital, UK Data management and image procurement
None of the authors have any conflict of interest to declare.
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT Cutaneous Vasculitis
Presentation A 20 year old gentleman presented in September 2014 with an erythematous maculo-papular rash distributed over his lower limbs, trunk & upper limbs. He had
RI PT
been on adalimumab (Humira, Abbvie, USA), 40 mg fortnightly for dual indication of Crohn's disease and Juvenile Idiopathic arthritis (JIA) since September 2010. He had been in remission from both conditions for over three years.
His blood tests showed raised inflammatory markers but no other abnormality, and a
SC
vasculitis screen was negative.
Progress
M AN U
He had dramatic worsening of rash over a week in hospital with rapid development of new lesions & bullous transformation of some of the existing lesions with necrotic areas.
A skin biopsy confirmed severe cutaneous leucocytoclastic vasculitis. He was treated with high-dose IV methylprednisolone 1 gram once/day for 5 days followed by oral prednisolone 60mg once/day which was tapered over the next 10 weeks. He
TE D
improved with this regimen. There was no specific trigger identified for sudden eruption of lesions. There was consensus among all teams managing him that the most likely cause of cutaneous vasculitis was anti-TNF therapy. We considered checking adalimumab levels but there were no studies demonstrating correlation between anti-TNF drug levels and cutaneous reactions, and the test was
AC C
Discussion
EP
not available locally.
Cutaneous vasculitis is thought to be a very rare adverse effect to adalimumab. There have been very few case reports of cutaneous vasculitis secondary to antiTNF therapy with an average duration of 36 months on treatment prior to developing a reaction, with all responding to drug withdrawal. 1, 3 We believe, to the best of our knowledge that this is the first reported case of bullous vasculitis of this degree of severity, secondary to adalimumab. (Pictures 1-5) The current literature about vasculitis secondary to anti-TNF therapy is scarce. One study reported that when patients who had confirmed cutaneous vasculitis were re-challenged with the same anti-TNF drug, the relapse rate was as high as 67 %.1, 4 The relapse rate was 33% in another study with an alternative anti TNF.1, 5 Therefore
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT we do not plan to use an anti-TNF agent again in our patient. The alternatives approved in the UK for use in adults with JIA but not for Crohn’s disease are Abatacept (IL-1inhibitor) and Rituximab (B-cell monoclonal antibody). The patient has
RI PT
not had a relapse of symptoms related to Crohn’s disease or JIA.
Conclusion
As the use of anti-TNF drugs increases worldwide, it is worth considering them as a possible cause of cutaneous vasculitic lesions. Our experience suggests that
SC
withdrawal of drug and high-dose corticosteroids is an effective treatment strategy. .
M AN U
References
1. Vasculitis associated with tumor necrosis factor-α inhibitors. Sokumbi O, Wetter DA, Makol A, Warrington KJ. Mayo Clin Proc. 2012 Aug; 87(8):739-45.
EP
TE D
2. Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists. Hawryluk EB, Linskey KR, Duncan LM, Nazarian RM. J Cutan Pathol. 2012 May; 39(5):481-92.
AC C
3. Cutaneous reactions to adalimumab administration. Downes MR, Prendiville S, Kiely C, Lenane P, Mulligan N. Ir Med J. 2011 Apr; 104(4):122-3.
4. Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents. Mohan N., Edwards E.T., Cupps T.R J Rheumatol. 2004;31(10):1955–1958
5. Vasculitides induced by TNFα antagonists: a study in 39 patients in France. Saint Marcoux B., De Bandt M., CRI (Club Rhumatismes et Inflammation) Joint Bone Spine. 2006;73(6):710–713
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT Acknowledgements We would like to acknowledge all clinicians and staff involved in managing the
AC C
EP
TE D
M AN U
SC
RI PT
patient. Our thanks to Consultants Dr.Cox, Dr.Desai, Dr.Hughes and Dr.Kasturi.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
PII: DOI: Reference:
S1542-3565(15)00666-7 10.1016/j.cgh.2015.05.012 YJCGH 54293
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 8 May 2015 Please cite this article as: Shivaji UN, Awasthi AK, Aherne R, Cutaneous Vasculitis secondary to Anti-TNF therapy A case report, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/ j.cgh.2015.05.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
Cutaneous Vasculitis
RI PT
ACCEPTED MANUSCRIPT
TE D
M AN U
SC
Cutaneous Vasculitis secondary to Anti-TNF therapy A case report
Submission of manuscript by:
AC C
EP
Dr.Uday N Shivaji (Corresponding author) Specialty Registrar in Gastroenterology Walsall Manor Hospital, UK Mob-00447908587589 Email- [email protected] Concept, reporting, writing and final approval
Dr.Ashish Kumar Awasthi Consultant Gastroenterologist Walsall Manor Hospital, UK Concept, critical revision and final approval Dr.Rebecca Aherne House Officer Walsall Manor Hospital, UK Data management and image procurement
None of the authors have any conflict of interest to declare.
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT Cutaneous Vasculitis
Presentation A 20 year old gentleman presented in September 2014 with an erythematous maculo-papular rash distributed over his lower limbs, trunk & upper limbs. He had
RI PT
been on adalimumab (Humira, Abbvie, USA), 40 mg fortnightly for dual indication of Crohn's disease and Juvenile Idiopathic arthritis (JIA) since September 2010. He had been in remission from both conditions for over three years.
His blood tests showed raised inflammatory markers but no other abnormality, and a
SC
vasculitis screen was negative.
Progress
M AN U
He had dramatic worsening of rash over a week in hospital with rapid development of new lesions & bullous transformation of some of the existing lesions with necrotic areas.
A skin biopsy confirmed severe cutaneous leucocytoclastic vasculitis. He was treated with high-dose IV methylprednisolone 1 gram once/day for 5 days followed by oral prednisolone 60mg once/day which was tapered over the next 10 weeks. He
TE D
improved with this regimen. There was no specific trigger identified for sudden eruption of lesions. There was consensus among all teams managing him that the most likely cause of cutaneous vasculitis was anti-TNF therapy. We considered checking adalimumab levels but there were no studies demonstrating correlation between anti-TNF drug levels and cutaneous reactions, and the test was
AC C
Discussion
EP
not available locally.
Cutaneous vasculitis is thought to be a very rare adverse effect to adalimumab. There have been very few case reports of cutaneous vasculitis secondary to antiTNF therapy with an average duration of 36 months on treatment prior to developing a reaction, with all responding to drug withdrawal. 1, 3 We believe, to the best of our knowledge that this is the first reported case of bullous vasculitis of this degree of severity, secondary to adalimumab. (Pictures 1-5) The current literature about vasculitis secondary to anti-TNF therapy is scarce. One study reported that when patients who had confirmed cutaneous vasculitis were re-challenged with the same anti-TNF drug, the relapse rate was as high as 67 %.1, 4 The relapse rate was 33% in another study with an alternative anti TNF.1, 5 Therefore
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT we do not plan to use an anti-TNF agent again in our patient. The alternatives approved in the UK for use in adults with JIA but not for Crohn’s disease are Abatacept (IL-1inhibitor) and Rituximab (B-cell monoclonal antibody). The patient has
RI PT
not had a relapse of symptoms related to Crohn’s disease or JIA.
Conclusion
As the use of anti-TNF drugs increases worldwide, it is worth considering them as a possible cause of cutaneous vasculitic lesions. Our experience suggests that
SC
withdrawal of drug and high-dose corticosteroids is an effective treatment strategy. .
M AN U
References
1. Vasculitis associated with tumor necrosis factor-α inhibitors. Sokumbi O, Wetter DA, Makol A, Warrington KJ. Mayo Clin Proc. 2012 Aug; 87(8):739-45.
EP
TE D
2. Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists. Hawryluk EB, Linskey KR, Duncan LM, Nazarian RM. J Cutan Pathol. 2012 May; 39(5):481-92.
AC C
3. Cutaneous reactions to adalimumab administration. Downes MR, Prendiville S, Kiely C, Lenane P, Mulligan N. Ir Med J. 2011 Apr; 104(4):122-3.
4. Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents. Mohan N., Edwards E.T., Cupps T.R J Rheumatol. 2004;31(10):1955–1958
5. Vasculitides induced by TNFα antagonists: a study in 39 patients in France. Saint Marcoux B., De Bandt M., CRI (Club Rhumatismes et Inflammation) Joint Bone Spine. 2006;73(6):710–713
Cutaneous Vasculitis
ACCEPTED MANUSCRIPT Acknowledgements We would like to acknowledge all clinicians and staff involved in managing the
AC C
EP
TE D
M AN U
SC
RI PT
patient. Our thanks to Consultants Dr.Cox, Dr.Desai, Dr.Hughes and Dr.Kasturi.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
