Recent findings about antimalarials in cutaneous lupus erythematosus: What dermatologists should know.

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first-line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID-19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity.

Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases.

Dysregulation of Janus kinase (JAK) pathways from uncontrolled cytokine signaling comprises the pathological basis for many complex inflammatory cutaneous disorders. Oral JAK inhibitors, upadacitinib, tofacitinib, and baricitinib targeting JAK 1 and JAK 1/3, respectively, are currently US Food and Drug Administration (FDA)-approved for several rheumatic conditions. However, studies have shown that JAK-mediated signaling pathways are involved in many immune-related dermatologic conditions. As a result, for recalcitrant diseases, JAK inhibitors are potential alternative therapies due to their broad targeted inhibitory mechanisms. In this case series, we present the successful off-label treatment of 6 cases across dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease, which failed conventional therapies with upadacitinib or tofacitinib. In the 3 dermatomyositis cases, use of upadacitinib or tofacitinib demonstrated positive clinical outcomes, with no recurrent symptoms in cases where upadacitinib was used. In treatment-resistant hidradenitis suppurativa, upadacitinib demonstrated reduced systemic flares and moderate cutaneous symptom improvement. In the case of cutaneous Crohn’s disease, upadacitinib resulted in reduced cutaneous symptoms without new flares. Tofacitinib resulted in completed resolution of cutaneous symptoms in our patient’s case of cutaneous lupus erythematosus. JAK inhibitors upadacitinib and tofacitinib may be potential drug candidates in patients with treatment-resistant disease, especially in cases of inflammatory cutaneous conditions such as dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease. Further studies with larger sample sizes among these conditions are warranted to assess potential broader applicability of the positive results demonstrated in our patient cases. J Drugs Dermatol. 2023;22(12):1183-1190. doi:10.36849/JDD.7500.

Manifestation of subacute cutaneous lupus erythematosus during treatment with anti-PD-1 antibody cemiplimab - a case report.

Introduction: The anti-programmed cell death protein 1 (PD-1) antibody cemiplimab has shown promising results in the treatment of unresectable or metastatic squamous cell carcinoma, however, frequently leads to immune-related adverse events limiting therapy efficacy. Although cutaneous side effects are common, only very few cases of cutaneous lupus erythematosus have been reported under anti-PD-1 immunotherapy. So far, no case of cutaneous lupus has been described under treatment with cemiplimab. Case report: For the first time, we report the case of a patient with advanced squamous cell carcinoma, who developed clinical and histological findings in sun-exposed skin that were consistent with anti-SS-A/Ro antibody-positive subacute cutaneous lupus erythematosus (SCLE) under treatment with cemiplimab. Additionally, laboratory chemical analyses revealed a severe immune-related hepatitis without clinical symptoms. Both, the SCLE and the hepatitis, resolved after the administration of topical and systemic steroids and the discontinuation of anti-PD-1 therapy. Conclusion: Treatment with cemiplimab can be associated with the appearance of cutaneous lupus erythematosus in sun-exposed areas. Application of topical and systemic glucocorticoids can lead to a rapid resolution of the skin eruptions. Moreover, our case illustrates the possibility of simultaneously occurring severe immune-related adverse events. This highlights the importance of additional diagnostics to avoid overlooking additional immune-related adverse events.

Propofol Induced Subacute Cutaneous Lupus Erythematosus: A Case Report.

We report a case of a woman who experienced unexplained recurrent rashes of varying severity after multiple exposures to anesthesia, and then 2 successful surgeries under general anesthesia with no resultant rashes after removing propofol from her anesthetic plans. We infer her previous postanesthetic rashes were likely associated with drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) triggered by propofol.

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Subacute cutaneous lupus erythematosus as a rare complication of disease-modifying therapy administration in multiple sclerosis: case report.

BACKGROUND: Teriflunomide, the active metabolite of leflunomide, is a disease-modifying therapy drug used for the treatment of multiple sclerosis (MS), yet the complications associated with this drug remain not fully understood. Here we present the rare case of a 28-year-old female MS patient who developed subacute cutaneous lupus erythematosus (SCLE) following teriflunomide treatment. Though SCLE has been reported to be associated with leflunomide, the current report represents the first documented evidence demonstrating SCLE as a potential teriflunomide treatment-related complication. Additionally, a literature review on the leflunomide-induced SCLE was conducted to emphasize the association of SCLE with teriflunomide, specifically amongst the female demographic with a preexisting autoimmune diathesis. CASE PRESENTATION: A 28-year-old female first presented with MS symptoms in the left upper limb along with blurred vision in the left eye. Medical and family histories were unremarkable. The patient exhibited positive serum biomarkers including ANA, Ro/SSA, La/SSB, and Ro-52 antibodies. Relapsing-remitting MS was diagnosed according to the 2017 McDonald's diagnostic criteria, and remission was achieved upon intravenous administration of methylprednisolone followed by teriflunomide sequential therapy. Three months post-teriflunomide treatment, the patient developed multiple facial cutaneous lesions. SCLE was subsequently diagnosed and was attributed to treatment-related complication. Interventions include oral administration of hydroxychloroquine and tofacitinib citrate effectively resolved cutaneous lesions. Discontinuation of hydroxychloroquine and tofacitinib citrate treatment led to recurring SCLE symptoms under continuous teriflunomide treatment. Full remission of facial annular plaques was achieved after re-treatment with hydroxychloroquine and tofacitinib citrate. The patient's clinical condition remained stable in long-term outpatient follow-ups. CONCLUSIONS: As teriflunomide has become a standard disease-modifying therapy for MS, the current case report highlights the importance of monitoring treatment-related complications, specifically in relation to SCLE symptoms.

Atorvastatin-induced Lupus Erythematosus Tumidus: A Case Report and Literature Review.

Lupus erythematosus tumidus (LET) is a rare photosensitive skin disease classified as a separate subtype of cutaneous lupus erythematosus. Clinically, it is characterized by erythematous plaques on sun-exposed areas. Typical histopathological findings are perivascular and periadnexal lymphohistiocytic infiltrates and prominent mucin deposition in the dermis. Treatment is based on photoprotection, topical corticosteroids, and antimalarial drugs. The exact pathogenesis of the disease is unknown. Drugs are considered a minor risk factor for the development of LET. We present a case of a 56-year-old woman who developed LET after starting treatment with atorvastatin. We describe her clinical course and review the literature concerning the cutaneous adverse reactions induced by statin drugs. To our knowledge, this is the first case of statin-induced LET. We conclude that statins can induce LET and that it is important for clinicians to be aware of this potential adverse effect associated with statins.

Concurrent Interstitial Granulomatous Dermatitis and TNF-α Antagonist-Induced Lupus Syndrome Secondary to Adalimumab for Crohn's Disease.

Tumor necrosis factor (TNF) antagonists have revolutionized management for various autoimmune and inflammatory conditions, including rheumatoid arthritis (RA), inflammatory bowel disease, hidradenitis suppurativa, psoriatic arthritis, and plaque psoriasis. However, adverse effects may necessitate switching to another biologic with a different mechanism of action. Here we report TNF-α antagonist-induced lupus syndrome (TAILS) revealed by interstitial granulomatous dermatitis (IGD), in the atypical context of Crohn's disease (CD).

Insights into proton pump inhibitor-induced photosensitivity: An observational study in a tertiary photobiology service.

BACKGROUND: Proton pump inhibitors (PPIs) are extensively prescribed but may cause photosensitivity and drug-induced lupus erythematosus (DILE), which can be overlooked as the drug may have been taken for years prior to presentation. METHODS: We reviewed the clinical and investigation findings of patients diagnosed with PPI-induced photosensitivity, diagnosed through the Scottish Photobiology Service. RESULTS: We report 11 patients with median age of onset 61-years and mean duration of PPI ingestion of 5-years [DILE (n = 6), phototoxicity (n = 3) and drug-induced solar urticaria through a lupus mechanism (n = 2)]. Five had Anti-Ro antibodies (three also ANA positive). Predominantly UVA and visible light photosensitivity was observed on phototesting. DISCUSSION: PPIs are a reversible cause of photosensitivity and DILE. Time to onset from drug initiation to symptoms can be prolonged, so clinicians should have a high index of suspicion in those taking PPIs. Most are diagnosed through clinical assessment and lupus serology, with phototesting indicated if there is diagnostic uncertainty.

Proton pump inhibitors-related subacute cutaneous lupus erythematosus: Clinical characteristics, management, and outcome.

PURPOSE: Previous knowledge about the association between proton pump inhibitors (PPIs) exposure and subacute cutaneous lupus erythematosus (SCLE) was mainly based on limited case reports or few review studies. We aim to evaluate the clinical characteristics, management, and outcome in patients with PPIs-induced SCLE. METHODS: Case reports and case series from 2000 to December 31, 2021, on SCLE induced by PPIs were collected and retrospectively analyzed. RESULTS: A total of 29 patients (6 male and 23 female) were included from 19 studies, the median age was 61 years (range 19-85), and 65.5% of patients were ≥60 years old. 37.9% of patients had the history of autoimmune diseases. The incubation period of PPIs intro to SCLE was 6 weeks for PPI-naive patients and 2 weeks for those re-administration of PPIs. The most common symptoms were annular and polycyclic erythematous (74.1%), rash or maculopapular (48.1%), and scaly plaques (40.7%). Trunk (69.2%), extremities (69.2%), face (26.9%), chest (26.9%), and back (26.9%) were common involved locations. Antinuclear antibodies, anti-Ro/SSA antibodies, and anti-La/SSB antibodies were positive in 24 patients (82.8%), 24 patients (82.8%), and 6 patients (20.7%), respectively. Direct immunofluorescence was positive in 50% of cases. Complete clinical remission (92.6%) was observed (median time: 4 weeks) with discontinuation of PPIs and treatment of oral corticosteroids (61.1%), hydroxychloroquine (44.4%), or topical steroids (16.7%). CONCLUSION: PPIs-related SCLE is a rare adverse reaction based on clinical manifestations associated with immunological abnormalities and suggestive histological findings. PPIs should be suspected when considering possible culprits for drug-related SCLE.

Proton Pump Inhibitors Associated With Drug-Induced Lupus Erythematosus.

This descriptive case series investigates the potential association between the use of proton pump inhibitors and drug-induced lupus erythematosus in cases reported in 2 large pharmacovigilance databases.

Proton pump inhibitor induced subacute cutaneous lupus erythematosus: Clinical characteristics and outcomes.

BACKGROUND: There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). AIMS: To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. METHODS: We conducted a matched case-control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. RESULTS: Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group (p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8 months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. CONCLUSION: Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Radiation-induced subacute cutaneous lupus erythematosus.

We present an unusual case of radiation-induced subacute cutaneous lupus erythematosus (SCLE) occurring in a patient with non-Hodgkin lymphoma. Dermatologists should be aware of the ability of low-dose radiation treatment to induce a first presentation or flare of SCLE, with the possibility of extension of disease outside of the radiation field.