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. 2023 Apr 6:10:1161837.
doi: 10.3389/fmed.2023.1161837. eCollection 2023.

Clinical features of acute generalized exanthematous pustulosis caused by hydroxychloroquine in rheumatology patients and exploration of CARD14 gene mutations

Feng Luo  1 , Xue-Mei Yuan  1 , Hong Xiong  1 , Yu-Zheng Yang  1 , Chang-Ming Chen  2 , Wu-Kai Ma  1   2 , Xue-Ming Yao  1   2
Affiliations

Clinical features of acute generalized exanthematous pustulosis caused by hydroxychloroquine in rheumatology patients and exploration of CARD14 gene mutations

Feng Luo et al. Front Med (Lausanne). .

Abstract

Introduction: Acute generalized exanthematous pustulosis (AGEP) is a rare condition characterized by superficial pustules following drug ingestion or infection. Currently, there is no clear link between rheumatism and AGEP. It has been described that hydroxychloroquine (HCQ) is a rare cause of acute generalized epidermal necrolysis (AGEP). Presently, there are limited studies on HCQ-induced AGEP. We aimed to explore the clinical features and associated gene expression of AGEP induced after HCQ treatment exposure in rheumatology patients.

Methods: We assessed patients with HCQ-induced AGEP diagnosed at the Second Affiliated Hospital of Guizhou University of Chinese Medicine between January 1, 2017, and May 1, 2022. We also reviewed similar cases reported in specific databases.

Results: The study included five females (mean age, 40.2 years), and the mean time from initiation of HCQ treatment to symptom onset was 12.2 d. All patients received steroids and allergy medications after HCQ discontinuation, and the rash completely resolved within an average of 25.2 d. We performed whole exome sequencing and Sanger validation in our patient sample. CARD14 gene mutations were detected in three patients. Additionally, seven mutation sites were detected.

Discussion: HCQ-induced AGEP may have a longer latency period and regression time than AGEP induced by other drugs. Our patients all experienced CARD14 gene mutations. AGEP often resolves with topical therapy and drug discontinuation, although some cases require systemic steroid therapy. In the future, patients with rheumatism should pay attention to the effectiveness of HCQ during treatment and be aware of the associated skin toxicity.

Keywords: CARD14; acute generalized exanthematous pustulosis; gene mutation; gene sequencing; hydroxychloroquine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Rash before and after treatment. (A) Rash on the face; (B) rash on the hands; (C) rash on the legs; (D) rash on the back; (E) rash on the abdomen; (F) rash on the chest; (G) improvement in the rash on the legs; and (H) improvement in the rash on the back.
Figure 2
Figure 2
Histopathological examination of a skin biopsy from the left chest showed mild vacuolar degeneration of epidermal basal cells, varying numbers of neutrophil infiltrates in the superficial-deep dermis (mainly in the superficial dermis), and epidermal cavernous pustule formation (hematoxylin and eosin staining; original magnification, ×400).
Figure 3
Figure 3
Mutation sites detected in the samples.
See this image and copyright information in PMC

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