Assessment of Antimalarial Therapy in Patients Who Are Hypersensitive to Hydroxychloroquine | Infectious Diseases | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Sign In
Table.  Clinical Characteristics of Hydroxychloroquine-Hypersensitive Patients
Clinical Characteristics of Hydroxychloroquine-Hypersensitive Patients
1.
Fruchter  R, Kurtzman  DJB, Patel  M,  et al.  Characteristics and alternative treatment outcomes of antimalarial-refractory cutaneous lupus erythematosus.  JAMA Dermatol. 2017;153(9):937-939. doi:10.1001/jamadermatol.2017.1160PubMedGoogle ScholarCrossref
2.
Pelle  MT, Callen  JP.  Adverse cutaneous reactions to hydroxychloroquine are more common in patients with dermatomyositis than in patients with cutaneous lupus erythematosus.  Arch Dermatol. 2002;138(9):1231-1233. doi:10.1001/archderm.138.9.1231PubMedGoogle ScholarCrossref
3.
Soria  A, Barbaud  A, Assier  H,  et al; FISARD (French Investigators for Skin Adverse Reaction to Drugs).  Cutaneous adverse drug reactions with antimalarials and allergological skin tests.  Dermatology. 2015;231(4):353-359. doi:10.1159/000438787PubMedGoogle ScholarCrossref
4.
Matsuda  T, Ly  NTM, Kambe  N,  et al.  Early cutaneous eruptions after oral hydroxychloroquine in a lupus erythematosus patient: a case report and review of the published work.  J Dermatol. 2018;45(3):344-348. doi:10.1111/1346-8138.14156PubMedGoogle ScholarCrossref
5.
Plaquenil [package insert]. Laval, Quebec: Sanofi-Aventis Canada Inc; 2017.
6.
James  JA, Kim-Howard  XR, Bruner  BF,  et al.  Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus.  Lupus. 2007;16(6):401-409. doi:10.1177/0961203307078579PubMedGoogle ScholarCrossref
Research Letter
February 13, 2019

Assessment of Antimalarial Therapy in Patients Who Are Hypersensitive to Hydroxychloroquine

Author Affiliations
  • 1Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
  • 2Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Dermatol. 2019;155(4):491-493. doi:10.1001/jamadermatol.2018.5212

Antimalarial medications (AMs) including hydroxychloroquine, chloroquine, and quinacrine are effective and widely used in the treatment of autoimmune connective tissue diseases (CTDs), including cutaneous lupus erythematosus (CLE). Hydroxychloroquine is typically used as first-line treatment; however, in up to 45% of patients for whom hydroxychloroquine fails, chloroquine might offer a more effective alternative.1

Adverse cutaneous reactions to AMs are relatively common, particularly in patients with dermatomyositis, although robust data in other CTDs is lacking.2 Most commonly, cutaneous hypersensitivity manifests as a morbilliform drug eruption, although a variety of reactions have been characterized. Existing data regarding rechallenge of AM-hypersensitive patients with the same or alternative AM therapy is sparse. In 2 small studies, a total of 10 patients with various CTDs who developed cutaneous hypersensitivity to hydroxychloroquine were challenged with the same or an alternative AM.2,3 Overall, 30% of patients experienced hypersensitivity recurrence, with recurrence occurring in 1 of 5 patients who were rechallenged with the same AM and in 2 of 5 who were treated with a different AM. All patients who had hypersensitivity recurrence had either dermatomyositis or rheumatoid arthritis. Of the 2 patients with CLE, neither experienced hypersensitivity recurrence when rechallenged with hydroxychloroquine. Given the multiple advantages of AM therapy in various CTDs, further data supporting the feasibility of rechallenge or alternate AM therapy in hypersensitive patients are crucial. Similarly, continuation of hydroxychloroquine treatment through a nonsevere cutaneous adverse reaction resulted in resolution of the reaction and therapeutic improvement in a patient with systemic LE.4 This suggests that in nonsevere cutaneous adverse reactions without internal organ involvement, it may be safe to proceed cautiously with the same therapy.

Methods

This multi-institutional retrospective review was approved by the New York University School of Medicine and Partners Healthcare institutional review boards, waiving patient written informed consent for deidentified data. We evaluated alternative AMs in patients with lupus erythematosus (LE) who developed cutaneous hypersensitivity, most frequently characterized by a morbilliform drug eruption, to hydroxychloroquine. Inclusion criteria were a dermatologist- or rheumatologist-confirmed diagnosis of LE, failure of hydroxychloroquine due to hypersensitivity, discontinuation of hydroxychloroquine treatment, and treatment with an alternative AM for at least 4 weeks. Outcome measures were alternative AM tolerability and level of disease control.

Results

Eleven patients with systemic LE and/or CLE were identified with nonsevere cutaneous hypersensitivity to hydroxychloroquine. Nine patients were subsequently treated with chloroquine and 3 with quinacrine (Table). They all subsequently tolerated either chloroquine (n = 8) or quinacrine (n = 3). One patient had recurrence of hypersensitivity when treatment was switched to chloroquine but subsequently tolerated quinacrine. All patients with recorded disease outcome (n = 6) achieved moderate to complete clearance after treatment with the alternative AM.

Discussion

Overall, of the hydroxychloroquine-hypersensitive patients in this study (N = 11), 100% tolerated an alternative AM, with 8 tolerating chloroquine and 3 tolerating quinacrine. All patients with known disease outcomes experienced improvement with an alternative AM regimen. This study demonstrates that patients with LE appear to have a low rate of hypersensitivity recurrence with alternative AMs and show a favorable clinical response when treatment is transitioned to these agents. This is especially notable, given that the product monograph for hydroxychloroquine warns against the use of alternative AMs in hydroxychloroquine-hypersensitive patients.5 Furthermore, this study supports findings across a variety of drug classes of a low percentage of recurrence at oral rechallenge in cases of nonsevere cutaneous adverse reactions, and it also provides data showing resolution of cutaneous eruptions after offending drug treatment continuation.4 Alternative AM therapy may preclude the need for treatment with systemic agents that carry greater risks, such as immunosuppression, or the need for closer therapeutic monitoring. Furthermore, AMs provide unique benefits, such as photoprotective properties and disease modification of systemic disease in LE.6

This study is limited primarily by its size and retrospective design. Given that this study includes only patients with LE, the safety of alternative AMs may not be generalizable to other CTDs. To our knowledge, this study evaluates the largest cohort of patients with LE to date who have developed hypersensitivity to hydroxychloroquine and subsequently tolerated other AMs, lending additional support to the limited data supporting this clinical practice.

Back to top
Article Information

Accepted for Publication: November 21, 2018.

Corresponding Author: Alisa Femia, MD, The Ronald O. Perelman Department of Dermatology, New York University Langone Health, Ambulatory Care Center, 240 E 38th St, 11th and 12th Floors, New York, NY 10016 (alisa.femia@nyumc.org).

Published Online: February 13, 2019. doi:10.1001/jamadermatol.2018.5212

Author Contributions: Drs Vleugels and Femia had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Riley and Schwager are co–first authors. Drs Vleugels and Femia are co–last authors.

Study concept and design: Riley, Vleugels, Femia.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Schwager, Stern, Femia.

Critical revision of the manuscript for important intellectual content: Riley, Schwager, Vleugels, Femia.

Statistical analysis: Stern.

Administrative, technical, or material support: Schwager.

Study supervision: Riley, Schwager, Vleugels, Femia.

Conflict of Interest Disclosures: None reported.

References
1.
Fruchter  R, Kurtzman  DJB, Patel  M,  et al.  Characteristics and alternative treatment outcomes of antimalarial-refractory cutaneous lupus erythematosus.  JAMA Dermatol. 2017;153(9):937-939. doi:10.1001/jamadermatol.2017.1160PubMedGoogle ScholarCrossref
2.
Pelle  MT, Callen  JP.  Adverse cutaneous reactions to hydroxychloroquine are more common in patients with dermatomyositis than in patients with cutaneous lupus erythematosus.  Arch Dermatol. 2002;138(9):1231-1233. doi:10.1001/archderm.138.9.1231PubMedGoogle ScholarCrossref
3.
Soria  A, Barbaud  A, Assier  H,  et al; FISARD (French Investigators for Skin Adverse Reaction to Drugs).  Cutaneous adverse drug reactions with antimalarials and allergological skin tests.  Dermatology. 2015;231(4):353-359. doi:10.1159/000438787PubMedGoogle ScholarCrossref
4.
Matsuda  T, Ly  NTM, Kambe  N,  et al.  Early cutaneous eruptions after oral hydroxychloroquine in a lupus erythematosus patient: a case report and review of the published work.  J Dermatol. 2018;45(3):344-348. doi:10.1111/1346-8138.14156PubMedGoogle ScholarCrossref
5.
Plaquenil [package insert]. Laval, Quebec: Sanofi-Aventis Canada Inc; 2017.
6.
James  JA, Kim-Howard  XR, Bruner  BF,  et al.  Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus.  Lupus. 2007;16(6):401-409. doi:10.1177/0961203307078579PubMedGoogle ScholarCrossref
×