Letters To The Editor Open Access
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Mar 27, 2017; 7(1): 9-10
Published online Mar 27, 2017. doi: 10.5411/wji.v7.i1.9
Penicillamine and auto-immunity: Relationship or coincidence?
Sofia Santos, Raquel Faria
Sofia Santos, Department of Nephrology, Centro Hospitalar do Porto, 4099-001 Porto, Portugal
Raquel Faria, Department of Medicine, Centro Hospitalar do Porto, 4099-001 Porto, Portugal
Author contributions: Both authors wrote this letter.
Conflict-of-interest statement: None of the authors has any potential conflicts of interest related to this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sofia Santos, MD, Department of Nephrology, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. sofia.fersantos@gmail.com
Telephone: +351-22-2077500 Fax: +351-22-2033189
Received: November 5, 2016
Peer-review started: November 9, 2016
First decision: November 30, 2016
Revised: December 2, 2016
Accepted: December 27, 2016
Article in press: December 28, 2016
Published online: March 27, 2017


Drug induced lupus is an established and recognised entity, and penicillamine is one of the drugs that induce it. But the uncertainty remains: Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?

Key Words: Penicillamine, Auto-immunity, Drug induced lupus

Core tip: Penicillamine and auto-immunity: Relationship or coincidence?


Due to its metal chelation properties D-penicillamine is widely used for the treatment of some human diseases, such as Wilson’s disease. However, many adverse reactions have been repeatedly reported to its use and it has been frequently described as an autoimmunity inducer, including drug-induced lupus (DI-L)[1]. There is evidence that penicillamine binds to aldehydes on the surface of macrophages and this leads to their activation, which in some patients can lead to an autoimmune syndrome[2]. Also, studies suggest that Th17 cells are involved in the pathogenesis of this penicillamine-induced auto-immunity[3]. We can inquire about the mechanism of this interaction: Whether we face a drug reaction that results in a specific autoimmune-like disease; or instead this drug plays its role prompting autoimmunity in an unspecific way.

The authors present two cases that highlight this doubt.

Case 1, a 20-year-old woman was treated with D-penicillamine for Wilson’s disease for seven years. She developed complaints of symmetrical joint pain, constitutional symptoms and alopecia. The blood test revealed anemia (7.1 g/dL), leucopenia (2900/μL), speckled anti-nuclear antibody 1/1280, positive antihistone antibodies, anti-dsDNA and anti-Smith. It was assumed as DI-L and she stopped D-penicillamine. Nevertheless the disease progressed in the next six years with sustained arthritis, purpura, Raynaud’s phenomenon and renal involvement: proteinuria 4.5 g per 24 h plus red blood cells, increasing serum creatinine, and complement consumption. The renal biopsy performed 6 years after suspension of D-penicillamine established the diagnosis class III lupus nephritis (ISN/RPS). Even though drug induced lupus erythematosus has some features in common with systemic lupus erythematosus (SLE), they are distinct entities. In this case, the clinical course led us to the diagnosis of de novo SLE. To our knowledge there is only one previous case report that shows a similar description[4].

Case 2, a 39-year-old woman who at the age of fourteen had a diagnosis of Wilson’s disease. After 18 years of treatment with D-penicillamine she started a polyarticular disease with a gradual onset and migratory joint involvement, specially metacarpophalangeal and proximal interphalangeal joints, as well as wrists and ankles. The immunological study showed high positive rheumatoide factor and anti-citrullinated protein antibodies. Also in this case, in spite of the withdrawal of D-penicillamine therapy there was progression of the clinical features. To our knowledge there is no other report in clinical literature that connects seropositive rheumatoid arthritis and Wilson’s disease with penicillamine-induced disease.

DI-L is an established and recognised entity, and penicillamine is one of the drugs that induce it. But the uncertainty remains: Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?


Manuscript source: Unsolicited manuscript

Specialty type: Immunology

Country of origin: Portugal

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B, B

Grade C (Good): C

Grade D (Fair): D

Grade E (Poor): 0

P- Reviewer: Di Genaro MS, Kwon HJ, La Cava A, Sisto M, Yankee T S- Editor: Ji FF L- Editor: A E- Editor: Li D

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