Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

INTRAVITREAL DEXAMETHASONE FOR THE TREATMENT OF MACULAR EDEMA SECONDARY TO HYDROXYCHLOROQUINE TOXICITY.

PURPOSE: Cystoid macular edema is a vision-threatening complication infrequently associated with hydroxychloroquine retinal toxicity. There are limited data on the best treatment for this pathology. METHODS: A retrospective case series is presented. RESULTS: In this series, we present three cases of cystoid macular edema in patients with diagnosed hydroxychloroquine maculopathy successfully treated with intravitreal dexamethasone implantation. CONCLUSION: Minimal literature has been published regarding the best management of cystoid macular edema related to hydroxychloroquine toxicity. Our case series suggests a possible new agent in the treatment of this rare occurrence.

Hydroxychloroquine had neutral effect on long-term risk of malignancy in rheumatoid arthritis patients: A population-based retrospective cohort study.

BACKGROUND: The cancer risk in rheumatoid arthritis (RA) patients has been discussed. Hydroxychloroquine (HCQ) may exert protective effects against malignancy. The study investigated the association between HCQ use and the risk of subsequent malignancy in RA patients. METHODS: Catastrophic illness certificated RA patients were extracted from the National Health Insurance Research Database. The index date was set 180 days after the RA diagnosis date to avoid immortal time bias. Two groups were matched in a 1-to-1 ratio by propensity score regarding age, gender, index date, relevant comorbidities, and comedication. HCQ users prior to the diagnosis of RA were exempted to ensure compliance with the new-user design. Cancers diagnosed before or less than 180 days after the index date were excluded to mitigate protopathic bias. The study adopted the Kaplan-Meier curve and Cox proportional hazards model to examine the association between HCQ use and cancer risk. The assumption of proportional hazard was also tested. RESULTS: Based on strict criteria, we included 492 eligible RA patients and divided them into study and control groups (N = 246 in each group). HCQ users exhibited a neutral risk of cancer relative to the controls (adjusted hazard ratio, 0.99; 95% CI, 0.44-2.21, p > .05). The assumption of proportional hazard was not violated. CONCLUSION: This study does not observe the effect of using HCQ as a primary regimen to prevent cancer in RA patients. We are assured that HCQ is not associated with an increased risk of subsequent malignancy in RA patients. Further mechanistic research is needed.

Hydroxychloroquine exacerbates imiquimod-induced psoriasis-like dermatitis through stimulating overexpression of IL-6 in keratinocytes.

OBJECTIVE: Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. METHODS: Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing. RESULTS: In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b+IL23+ dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells. CONCLUSIONS: HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin. KEY MESSAGES: This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model.

Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers.

Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas-entrapping material containing CO in a pre-clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.

Evaluation of the efficacy and safety of oral N-acetylcysteine in patients with COVID-19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial.

BACKGROUND: The current absence of gold-standard or all-aspect favorable therapies for COVID-19 renders a focus on multipotential drugs proposed to prevent or treat this infection or ameliorate its signs and symptoms vitally important. The present well-designed randomized controlled trial (RCT) sought to evaluate the efficacy and safety of N-acetylcysteine (NAC) as adjuvant therapy for 60 hospitalized Iranian patients with COVID-19. METHODS: Two 30-person diets, comprising 15 single diets of Kaletra (lopinavir/ritonavir) + hydroxychloroquine (HCQ) with/without NAC (600 mg TDS) and atazanavir/ritonavir + HCQ with/without NAC (600 mg TDS), were administered in the study. RESULTS: At the end of the study, a further decrease in C-reactive protein was observed in the NAC group (P = 0.008), and no death occurred in the atazanavir/ritonavir + HCQ + NAC group, showing that the combination of these drugs may reduce mortality. The atazanavir/ritonavir + HCQ and atazanavir/ritonavir + NAC groups exhibited the highest O2 saturation at the end of the study and a significant rise in O2 saturation following intervention commencement, including NAC (P > 0.05). Accordingly, oral or intravenous NAC, if indicated, may enhance O2 saturation, blunt the inflammation trend (by reducing C-reactive protein), and lower mortality in hospitalized patients with COVID-19. CONCLUSION: The NAC could be more effective as prophylactic or adjuvant therapy in stable non-severe cases of COVID-19 with a particularly positive role in the augmentation of O2 saturation and faster reduction of the CRP level and inflammation or could be effective for better controlling of COVID-19 or its therapy-related side effects.

Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease.

Importance: Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD). Objectives: To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine. Design, Setting, and Participants: This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine. Exposure: Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d). Main Outcome and Measure: The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression. Results: In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome. Conclusions and Relevance: In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.

Pharmacogenomics of chloroquine and hydroxychloroquine: current evidence and future implications.

As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some CYP3A5, CYP2D6 and CYP2C8 genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.

Increased skin reactions with hydroxychloroquine during breast radiotherapy.

With the advances in radiation technology, skin reaction due to postoperative radiotherapy (RT) in breast cancer patients is generally mild and tolerable. However, certain drugs may increase the radiation effect. In literature, only few cases of adverse reactions in the radiation field have been reported with the use of Chloroquine. This report describes the case of a 30-year-old young female who had enhanced skin reactions with hydroxychloroquine (HCQ) treatment during breast RT. HCQ should be used with caution in patients undergoing RT due to its potential radiosensitizer effect.

Protective Effect of Quercetin and p-Coumaric Acid (p-CA) Against Cardiotoxicity: An In Silico Study.

BACKGROUND: Hydroxychloroquine (HCQ) is a common antimalarial drug that has been used effectively in the treatment of various rheumatic and auto-immunity diseases. The major side effects and drawbacks associated with HCQ are cardiotoxicity, retinopathy, gastrointestinal upset, and neuromyopathy however, cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by HCQ. The present work is focused on receptor and signaling molecules associated with pathways attributing to drug-induced cardiotoxicity. We analyzed the therapeutic efficacy of selected natural products in HCQ-induced cardiotoxicity through insilico. We selected Syzygium cumini polyphenols, quercetin, and p-coumaric acid. The motivation behind selecting quercetin, and p-coumaric acid is their wide applicability as an antioxidative, anti-inflammatory, antiapoptotic, and cardioprotective. METHODS: For predicting quercetin, p-coumaric acid, and HCQ toxicity and physicochemical properties, in silico studies were performed using ProTox II and Swiss ADME. We further performed molecular docking using Autodock Vina and Discovery Studio visualizer to find the affinity of selected polyphenols against signaling molecules and receptors. Then we performed network pharmacological studies of selected signaling molecules. RESULTS: We analyzed that the computational method indicated quercetin (Δ G -9.3 kcal/mol) has greater binding affinity than p-Coumaric acid for prevention and restoration of the disease while hydroxychloroquine was taken as a control. CONCLUSION: It can be concluded that Syzygium cumini, polyphenols may aid in the future therapeutic potential against HCQ-induced cardiotoxicity.

A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer.

BACKGROUND: In RAS-mutant tumors, combined MEK and autophagy inhibition using chloroquine demonstrated synthetic lethality in preclinical studies. This phase II trial evaluated the safety and activity of the MEK inhibitor binimetinib combined with hydroxychloroquine (HCQ) in patients with advanced KRAS-mutant non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included KRAS-mutant NSCLC, progression after first-line therapy, ECOG PS 0-1, and adequate end-organ function. Binimetinib 45 mg was administered orally (p.o.) bid with HCQ 400 mg p.o. bid. The primary endpoint was objective response rate (ORR). A Simon's 2-stage phase II clinical trial design was used, with an α error of 5% and a power ß of 80%, anticipating an ORR of 30% to proceed to the 2-stage expansion. RESULTS: Between April 2021 and January 2022, 9 patients were enrolled to stage I: median age 64 years, 44.4% females, 78% smokers. The best response was stable disease in one patient (11.1%). The median progression free survival (PFS) was 1.9 months, and median overall survival (OS) was 5.3 months. Overall, 5 patients (55.6%) developed a grade 3 adverse event (AE). The most common grade 3 toxicity was rash (33%). Pre-specified criteria for stopping the trial early due to lack of efficacy were met. CONCLUSION: The combination of B + HCQ in second- or later-line treatment of patients with advanced KRAS-mutant NSCLC did not show significant antitumor activity. (ClinicalTrials.gov Identifier: NCT04735068).

Endomyocardial biopsy-proven hydroxychloroquine-induced cardiomyopathy in a patient with rheumatoid arthritis.

Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions. Its long-term use is well-known to have toxic effects on cardiac muscle cells. We present a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. The patient was referred to our heart failure clinic for concerns of reduction in left ventricular ejection fraction despite being on guideline-directed medical therapy. She had been diagnosed with rheumatoid arthritis, pulmonary hypertension and then subsequently heart failure with reduced ejection fraction 5 years ago. The evaluation included right heart catheterisation, cardiac MRI and endomyocardial biopsy. Light and electron microscopy showed myocyte hypertrophy and vacuolar change, abnormal mitochondria, myeloid bodies and curvilinear bodies. These findings were specific for hydroxychloroquine-induced cardiomyopathy. This case highlights the importance of clinical monitoring, early suspicion and consideration of drug-induced toxicities as a culprit for heart failure.

Pharmacovigilance follow-up of patients in the context of the COVID-19 pandemic.

INTRODUCTION: In the context of COVID-19 pandemic, a national pharmacovigilance survey was set up in March 2020. The purpose of this survey was to ensure continuous monitoring of adverse drug reactions (ADRs) in patients with COVID-19, not only related to the drugs used in this indication but also related to all drugs administered to these patients or suspected of having promoted the infection. MATERIAL AND METHODS: This descriptive study was based on data extracted from the French Pharmacovigilance Database from 1 January 2020 to 30 September 2021. Misuse was also analysed through the MESANGE project. The ADRs were classified according to three groups: "drugs used to treat COVID-19", "other drugs administered to COVID-19 positive patients" and "drugs suspected of having promoted COVID-19". The data were also presented according to 2 periods (period one was from January to June 2020 and period two from July 2020 onwards). RESULTS: Among 2189 included cases, 67.1% were serious. Cases were mainly related to "other drugs administrated to COVID-19 positive patients" (58.5%) followed by "drugs used to treat COVID-19" (33.7%) and "drugs suspected of having promoted COVID-19" (7.8%). Drugs used to treat COVID-19 and their main safety profile were different depending on the period: mostly hydroxychloroquine (51%) with heart injury and lopinavir/ritonavir (42%) with liver injury for the first period, and dexamethasone (46%) with hyperglycemia and tocilizumab (28%) with liver injury for the second period. The drugs suspected of worsening COVID-19 differed in both periods especially for non-steroidal anti-inflammatory drugs mainly reported in period 1 (41.5% versus 8.2% in period 2). Other immunosuppressive drugs were in the majority in the second period (85.7%), with mainly methotrexate (15.3%), anti-CD20 (15.3%) and anti-TNF alpha (10.5%). No confirmed safety signal was identified among other drugs administered to patients with COVID-19. The profile of ADRs and suspected drugs was similar between the 2 periods. The study of misuse in outpatient settings identified in both periods mainly hydroxychloroquine, azithromycin, ivermectin and zinc±vitamin C. DISCUSSION: This survey, based on real-time pharmacological and medical assessment of ADRs and weekly meetings in a specific national committee, made it possible to identify relevant safety signals which contribute to patient care with no delay. The main safety signal highlighted was serious cardiac damage under hydroxychloroquine, alone or combined with azithromycin and also with lopinavir/ritonavir. This signal has contributed to the evolution of the recommendations for these 2 drugs. The methodology of this survey has been taken over and is still going on for the pharmacovigilance monitoring of vaccines against COVID-19, for monoclonal antibodies used against COVID-19 and also for Paxlovid® (nirmatrelvir/ritonavir) which benefit from dedicated surveys.

Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight-based dose at the HCQ start date was the main exposure of interest. The outcome was incident all-cause heart failure with reduced ejection fraction (HFrEF), life-threatening arrhythmia, or cardiac death. We used Fine-Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. RESULTS: Of 294 patients, 37 (13%) developed the outcome over a median follow-up time of 7.9 years (interquartile range [IQR] 4.2-12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight-based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41-0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53-1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. CONCLUSION: Higher HCQ doses were not associated with an increased risk of HFrEF, life-threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.

Unusual Presentation of Acute Hydroxychloroquine Retinopathy.

PURPOSE: To report a rare case of cystoid macular edema (CME) as a presentation of acute hydroxychloroquine-related retinal toxicity. OBSERVATIONS: A 37-year-old female patient visited our ophthalmology department in October 2019 complaining of bilateral blurred vision and metamorphopsia for 3 days. Best-corrected visual acuity (BCVA) was 6/6 in the right eye and 6/7.5 in the left eye under the Snellen E chart. Before presentation, she had taken hydroxychloroquine as a "reproduction-facilitating medication" prior to the in vitro fertilization (IVF) procedures with the daily dose of 200 mg for 1 week in March 2019 and 400 mg for 1 month in September 2019. She also took a combination of several herbal medicine including "Angelica sinensis" for 6 months in this period. On examination, typical signs of hydroxychloroquine maculopathy such as bilateral paracentral retinal pigment epithelium (RPE) change in blue autofluorescence and loss of the paracentral ellipsoid zone in optical coherence tomography ("flying saucer sign") were noted. CME was also found in fluorescein angiography. Her symptoms improved gradually after cessation of hydroxychloroquine and herb medicine without any further treatment. Resolution of bilateral CME was revealed at 16 weeks with final bilateral BCVA 6/6. CONCLUSIONS AND IMPORTANCE: Although rare, acute hydroxychloroquine maculopathy could occur in patients with concomitant usage of medications that could interfere with P450 enzymes system. Careful acquisition of drug history and serial ophthalmological examinations are advised in using hydroxychloroquine for disease management even for a short period of time.

Hydroxychloroquine safety in Covid-19 vs non-Covid-19 patients: analysis of differences and potential interactions.

BACKGROUND: The use of hydroxychloroquine (HCQ) in the first COVID-19 epidemic wave raised safety concerns. RESEARCH DESIGN AND METHODS: Adverse reactions (ADR) suspected to be induced by HCQ and submitted to the Spanish Pharmacovigilance Database were studied. A disproportionality analysis was performed to determine adverse effects reported in non-Covid and Covid patients. To explore potential drug-drug interactions, Omega (Ω) statistics was calculated. RESULTS: More severe cases were reported when used in COVID-19. Main differences in frequency were observed in hepatobiliary, skin, gastrointestinal, eye, nervous system and heart ADRs. During the COVID-19 pandemic, high disproportionality in reports was found for Torsade de Pointes/QT prolongation with a ROR (-ROR) of 132.8 (76.7); severe hepatotoxicity, 18.7 (14.7); dyslipidaemias, 12.1 (6.1); shock, 9.5 (6.9) and ischemic colitis, 8.9 (2.6). Myopathies, hemolytic disorders and suicidal behavior increased their disproportionality during the pandemic. Disproportionality was observed for neoplasms, hematopoietic cytopaenias and interstitial lung disease in the pre-COVID-19 period. Potential interactions were showed between HCQ and azithromycin, ceftriaxone, lopinavir and tocilizumab. CONCLUSIONS: The use of HCQ during the Covid-19 pandemic changed its ADRs reporting profile. Of particular concern during the pandemic were arrhythmias, hepatotoxicity, severe skin reactions and suicide, but not ocular disorders. Some signals identified would require more detailed analyses.

[Exogenously induced retinopathies]. / Exogen bedingte Retinopathien.

Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the effects are transient, whereas other effects induce irreversible toxic reactions. Retinal damage may develop either acutely with obvious relation to the damaging cause, but often may take a long duration of repeated use of a substance or medication. External stimulants (e.g. nicotine, alcohol, poppers, methanol) are the most frequent cause of exogenously induced retinal damage. Side effects from systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK-, ERK-, FLT3-, checkpoint inhibitors, didanosin, pentosanpolysulfat sodium) or intravitreally applied drugs (e.g. antibiotics, VEGF-inhibitors) are less frequent. Ocular side effects associated with vaccinations are rare. Ambient light sources induce no damaging effects on the retina. Incorrect use of technical or medical light sources (e.g. laser pointers) without adherence to safety recommendations or unshielded observation of the sun might induce permanent retinal damage. Local or external irradiation might induce retinal vascular damage resulting in radiation retinopathy.

Drug rash with eosinophilia and systemic symptoms syndrome masquerading as a lymphoproliferative disorder in a young adult on immunosuppressive therapy for rheumatoid arthritis: a case report.

BACKGROUND: This case reveals a novel presentation of drug rash with eosinophilia and systemic symptoms syndrome that mimics a lymphoproliferative disorder. The heterogeneous clinical presentation of drug rash with eosinophilia and systemic symptoms syndrome gives rise to a broad differential diagnosis that includes a multitude of infectious, inflammatory, and autoimmune conditions. This patient was diagnosed with drug rash with eosinophilia and systemic symptoms syndrome 4 weeks after starting sulfasalazine and 5 weeks after starting hydroxychloroquine for rheumatoid arthritis. Both of these medications have been shown to cause drug rash with eosinophilia and systemic symptoms syndrome, albeit more rarely in the context of hydroxychloroquine. This patient's history, physical examination, and workup illuminate a case of drug rash with eosinophilia and systemic symptoms syndrome that masquerades as a lymphoproliferative disorder despite its adherence to the RegiSCAR criteria. CASE PRESENTATION: A 22-year-old African-American female with an atopic history and rheumatoid arthritis presented for evaluation of a rash, unremitting fevers, and syncope. She was found to have drug rash with eosinophilia and systemic symptoms syndrome. A syncope workup was unremarkable. Computed tomography of the chest/abdomen/pelvis confirmed extensive lymphadenopathy and revealed a small right pleural effusion (Fig. 5). These imaging findings accompanied by fevers and a rash in the setting of eosinophilia, leukocytosis, and transaminitis led to the clinical suspicion for drug rash with eosinophilia and systemic symptoms syndrome. Steroids were subsequently initiated. Broad-spectrum antibiotic therapy was implemented to cover for possible skin/soft tissue infection due to initial paradoxical worsening after discontinuation of the culprit drugs. Lymph node biopsy ruled out a lymphoproliferative disorder and instead demonstrated necrotizing lymphadenitis. An extensive infectious and autoimmune workup was noncontributory. Clinical improvement was visualized, antibiotics were discontinued, and she was discharged on a steroid taper. CONCLUSION: This case reflects how drug rash with eosinophilia and systemic symptoms syndrome can masquerade as a lymphoproliferative disorder. Additionally, it highlights the extent to which rapid identification and treatment optimized the patient's outcome. It calls into question how immunogenetics may factor into a patient's susceptibility to acquire drug rash with eosinophilia and systemic symptoms syndrome. This case is unique because of the early onset of visceral organ involvement, the type of internal organ involvement, the hematopoietic features, and the lymphadenopathy associated with a disease-modifying antirheumatic drug.

Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares.

This study of an academic medical center patient cohort with systemic lupus erythematosus (SLE) investigates the association between hydroxychloroquine dose based on current guidelines and risk of lupus flares.