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Drug-Induced Cutaneous Lupus Erythematosus: 88 New Cases Background: Drug-Induced Subacute Cutaneous Lupus Erythematosusrecognition (DI-SCLE)

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Drug-Induced Cutaneous Lupus Erythematosus: 88 New Cases Background: Drug-Induced Subacute Cutaneous Lupus Erythematosusrecognition (DI-SCLE) Clinical report Eur J Dermatol 2017; 27(1): 28-33 Rasa LAURINAVICIENE Drug-induced cutaneous lupus erythematosus: Linda Holm SANDHOLDT Anette BYGUM 88 new cases Department of Dermatology and Allergy Centre, Odense University Hospital, Background: An increasing number of drugs have been linked to DK-5000, Odense C, Denmark drug-induced subacute cutaneous lupus erythematosus (DI-SCLE). The Reprints: R. Laurinaviciene recognition and management of DI-SCLE can be challenging, as the <[email protected]> condition may be triggered by different classes of drugs after variable lengths of time. Objectives. To determine the proportion of patients with cutaneous lupus erythematosus (CLE) whose drugs are an inducing or aggravating factor. Materials & methods: We conducted a retrospec- tive chart review of patients diagnosed with CLE at a dermatological department over a 21-year period. We registered clinical, serological, and histological data with a focus on drug intake. Results: Of 775 consec- utive patients with a diagnosis of lupus erythematosus (LE) or suspected LE, a diagnosis of CLE could be confirmed in 448 patients. A total of 130 patients had a drug intake that could suggest DI-SCLE. In 88 cases, a drug was evaluated to be definitely, probably, or possibly trigger- ing CLE using the Naranjo probability scale. The most common drugs involved were proton pump inhibitors (PPIs), thiazide diuretics, anti- fungals, chemotherapeutics, statins, and antiepileptics. The incubation period varied widely with a median of eight weeks. The characteristics of DI-SCLE patients were more widespread rash relative to the other patients, with inflamed skin lesions or atypical variants which could resemble erythema multiforme. Conclusions: We present 88 patients with DI-SCLE, which is the largest case series reported, to date. DI- SCLE represented 20% of patients with CLE seen at our department. We conclude that DI-SCLE should be considered in every case of SCLE. Key words: cutaneous lupus erythematosus, drug-induced cutaneous Article accepted on 30/6/2016 lupus erythematosus, drug reactions arious drugs can induce the development of ies are usually present, whereas anti-histone antibodies are autoantibodies and clinical features of LE, similar rarely found. DI-SCLE can be seen de novo in patients with- V to systemic lupus erythematosus (SLE) or cuta- out former CLE or can present as a cutaneous lupus flare in neous lupus erythematosus (CLE). There are currently no a patient with already known CLE. Incidents of DI-SCLE standard diagnostic criteria for drug-induced lupus ery- are unknown. To date, more than 165 cases of DI-SCLE thematosus (DILE), although it has been defined as a have been published in the English literature [6-26]. lupus-like syndrome related to continuous drug exposure, A number of different drug categories have been associated which resolves after discontinuation of the drug [1, 2]. It has with DILE and DI-SCLE, respectively. been estimated that 10-15% of SLE cases are drug induced The drugs most frequently associated with development and that 15,000-30,000 cases of drug-induced systemic of DI-SLE are hydralazine, procainamide, isoniazid, and lupus erythematosus (DI-SLE) may occur in the United minocycline [1, 5]. DI-SCLE was first reported by Reed et States every year [1, 3-5]. al. in 1985, associated with hydrochlorothiazide [27]. To The skin manifestations of drug-related CLE are mostly of date, more than 50 drugs have been linked to DI-SCLE, the SCLE type and symptoms and serological features over- however, the most common triggers are antihypertensive lap with those of idiopathic SCLE. Both conditions usually agents, such as thiazide diuretics, calcium channel blockers present with annular polycyclic or papulosquamous skin and angiotensin-converting enzyme inhibitors, terbinafine, doi:10.1684/ejd.2016.2912 lesions, mostly on sun-exposed areas. However, in contrast proton pump inhibitors (PPIs), lipid lowering agents, or to the idiopathic form, the cutaneous manifestations of DI- chemotherapeutic agents [6, 26, 28]. Over the past decade, SCLE are often more widespread, e.g. with involvement of an increasing number of drugs in different classes have the lower legs and a tendency to have bullous or erythema been recognised as triggers for DILE and the number is multiforme-like skin lesions [2, 6]. Antinuclear antibodies constantly increasing, in proportion to the licensing of new (ANA) and anti-Ro/Sjögren’s syndrome A (SSA) antibod- medications on the market, such as TNF-␣ antagonists. 28 EJD, vol. 27, n◦ 1, January-February 2017 To cite this article: Laurinaviciene R, Sandholdt LH, Bygum A. Drug-induced cutaneous lupus erythematosus: 88 new cases. Eur J Dermatol 2017; 27(1): 28-33 doi:10.1684/ejd.2016.2912 Drug-induced chronic cutaneous lupus erythematosus Causality assessment (CCLE), which is rarely reported in the literature, usually refers to fluorouracil, non-steroidal anti-inflammatory We used the Naranjo algorithm to estimate the causal rela- drugs, and TNF-␣ antagonists, such as infliximab and tionship between drugs and cutaneous reactions in the adalimumab [1, 5, 29]. identified cases [30]. This scoring system consists of ten The diagnosis and management of DI-SCLE is usually sim- questions, answered as “yes”, “no”, or “do not know”, ple when the condition is recognised and the patient is resulting in a score to each question ranging from -1 to +2. taking only a single drug known to be a trigger for DI-SCLE. Based on the total score, the adverse drug reaction (ADR) In patients on multiple and essential drugs, the situation can is divided into the following probability categories: defi- be quite challenging. nite, probable, possible, or doubtful. Patients with doubtful The aim of this study was to determine the proportion of ADRs were excluded from this study and only patients with patients with CLE whose drugs were an inducing or aggra- definite, probable, or possible causality were analysed. vating factor, and to compare our findings with the current literature. Ethics Permission was obtained from the Danish Data Protection Agency, J.nr 2012-41-0927. Material and Methods Results Study design A retrospective chart review was conducted in patients with A total of 775 medical records were reviewed and we iden- CLE seen at the Department of Dermatology and Allergy tified 448 patients with CLE. A total of 130 of the 448 Centre, Odense University Hospital, Denmark, between patients had a drug intake that could suggest drug-related January 1994 and December 2014. Odense University Hos- CLE. Forty-two cases were excluded as doubtful and/or pital covers the region of southern Denmark, which has 1.2 due to insufficient data based on the medical records. In 88 million inhabitants. cases, the drug history was evaluated to be definitely, prob- ably, or possibly related to CLE, and their clinical data are presented in Annexe Atable S1. A summary of the char- Identifying cases acteristics of the 88 patients with DI-SCLE are presented in table 1. The remaining LE patients without drug-related Inclusion criteria were the following ICD-10 diag- factors were classified as idiopathic cases. noses: M32.0: drug-induced systemic lupus erythematosus; Fifty patients exhibited de novo DI-SCLE and 38 patients M32.1: systemic lupus erythematosus with organ or sys- had a previous history of CLE exacerbated by LE-triggering tem involvement; M32.2: other forms of systemic lupus drugs. With the probability score, we demonstrated that five erythematosus; M32.9: systemic lupus erythematosus, non- of the 88 patients had a definite, 53 had a probable, and 30 specified; L93.0: discoid lupus erythematosus (CCLE), had a possible drug/CLE relationship. The median age at lupus erythematosus not otherwise specified; L93.1: sub- the initial visit was 63 years (range: 28-91 years; mean: 61 acute cutaneous lupus erythematosus; and L93.2: other years). In total, 86% of the patients were female. local lupus erythematosus, lupus erythematosus profundus (lupus panniculitis), and lupus erythematosus tumidus. Medical records were reviewed to identify possible DI- Drugs implicated in DI-CLE SCLE cases. Since July 2007, all patients with CLE were also registered In the group of patients with definite/probable/possible DI- using the European Society of Cutaneous Lupus Erythe- CLE, 11 different drugs were implicated (figure 1). The matosus (EUSCLE) Core Set Questionnaire, leading to the identification of any sign or suspicion of DILE. Proton pump inhibitors Antihypertensives Antifungals Collection of data Chemotherapeutics Statins Medical records from patients using potential lupus- Antiepileptics triggering medications were analysed. In several cases, it Biologics was necessary to request additional information from gen- Antimalarials eral practitioners, other departments, or from the personal Antirheumatics Antibiotics electronic medicine profile collected in relation to their clin- Antidepressants ical course. The medical records were reviewed for clinical course, treatment, and histopathological findings. The fol- 0 5 10 15 20 25 30 lowing data were obtained from the hospital records: patient Number of patients with DI-CLE gender, age at first patient contact in relation to current rash, previous history of skin symptoms, latency and resolution period, medication information, objective findings, sero- Figure 1. Eighty-eight cases of drug-induced cutaneous lupus logical and histopathological data, as well as therapeutic erythematosus (DI-CLE) precipitated by 11 different classes measures. of
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