While chloroquine, a derivative of quinine, has been used as an antimalarial for 70 years, hydroxychloroquine is now used to treat conditions such as rheumatoid arthritis and systemic lupus erythem...

https://www.tandfonline.com/doi/pdf/10.1080/15563650.2020.1817479

Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose.

COVID-19 (coronavirus viral disease 2019), due to the novel SARS-CoV-2, may present with different types of cutaneous manifestations of varying pathophysiology. During the ongoing pandemic, publications reporting dermatologic findings in COVID-19 continue to emerge. Cutaneous vasculopathy and microthrombus-related changes including acral and sacral lesions, retiform purpura, livedo reticularis, and cutaneous vasculitis are notable findings in adult patients. Other exanthems include urticaria or angioedema, morbilliform/maculopapular exanthems, erythema multiforme, and vesicular eruptions. Increased recognition of these findings, especially those consistent with cutaneous microthrombi or vasculitis, is of particular importance. Additionally, occupational dermatologic disease related to extended personal protective equipment (PPE) use, such as skin damage and irritant or allergic contact dermatitis (ACD), represents another emerging problem amidst the pandemic. In this review, we highlight the various cutaneous manifestations associated with COVID-19 in adult patients and occupational dermatitis in health care workers (HCWs) caring for this patient population.

/pdf/cutaneous-manifestations-in-adult-patients-with-covid-19-and-4rc0j06bw8.pdf

Cutaneous Manifestations in Adult Patients with COVID-19 and Dermatologic Conditions Related to the COVID-19 Pandemic in Health Care Workers.

Novel dissolving microneedles preparation for synergistic melasma therapy: Combined effects of tranexamic acid and licorice extract

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP. 

/pdf/acute-generalized-exanthematous-pustulosis-clinical-features-dpeuqq23.pdf

Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management

Melasma is a disorder of hyperpigmentation and vascularization often found in women between the ages of 20 and 40. The pathogenesis is unknown, but melasma often occurs in sun‐exposed areas of the face, forearms, and back. Risk factors include family history, increased estrogen/progesterone, certain medications, and UV exposure. Melasma is typically treated with topical hydroquinone (HQ); however, it is often refractory to treatment. Tranexamic acid (TXA) is a plasmin inhibitor used off‐label in the treatment of melasma. TXA can be administered orally, topically, or intralesionally.

Tranexamic acid in melasma: A focused review on drug administration routes

There is a need for adjuvant imaging techniques that would allow reducing the number of slow Mohs stages. This study aimed to evaluate the use of dermoscopy in the demarcation of basal cell carcinoma (BCC) surgical margins for slow Mohs surgery. This was a retrospective study over 3 years (2016-2019), including patients with BCC excised using slow Mohs surgery. On the basis of the treatment received, the patients were divided into 2 groups: group 1 (28 BCC) and group 2 (26 BCC). In group 2, BCC margins were demarcated using dermoscopy. A total of 54 patients were enrolled in the study. The number of positive lateral margins was significantly lower in the group where BCC margins were demarcated using dermoscopy (19% vs 53%, P = 0.012). In this group, the number of Mohs stages needed to achieve complete clearance was significantly lower. However, the mean interval between the first Mohs excision and Mohs clearance wasn't significantly different between the 2 groups (9 ± 4 vs 12 ± 7 days). Preoperative dermoscopy is useful for reducing the number of positive lateral margins and the number of slow Mohs stages in treating BCC especially pigmented tumors. This article is protected by copyright. All rights reserved.

Effectiveness of Dermoscopy in the Demarcation of Surgical Margins in Slow Mohs Surgery.

Background Treatment options for erythematotelangiectatic rosacea (ETR) are still scarce. Tranexamic acid (TXA) is an antifibrinolytic drug that was recently used for the treatment of ETR. Aims to evaluate the efficacy and safety of intradermal microinjections of TXA for ETR. Patients/methods This was a retrospective study enrolling patients, treated with TXA intradermal microinjections for ETR, from January 2019 to February 2020. Response to treatment was assessed based on subjective symptoms, clinical photographs and the Investigator Global Assessment of Rosacea Severity Score (IGA-RSS). Results Six patients were included. The mean number of monthly intradermal TXA microinjections was 5.1±1.3. The mean decrease of IGA-RSS was 2.4±0.5. Local side effects, mainly transient erythema and swelling, were noticed in three cases. No systemic effects were noted. Clinical improvement, in respondent patients, lasted after 3 months of follow-up. Conclusion Intradermal TXA microinjections is a safe and effective treatment option for ETR. The optimal number of monthly sessions has yet to be determined.

Tranexamic acid microinjections : a novel treatment option for erythematotelangiectatic rosacea.

Introduction Several studies investigated the use of dermoscopy in the delineation of basal cell carcinoma (BCC) for Mohs micrographic surgery (MMS) with conflicting results. Objectives The purpose of this systematic review with meta-analysis was to evaluate the effectiveness of the use of dermoscopy-guided MMS in the treatment of BCC. Methods We included all comparative studies. Cases of BCC treated using dermoscopy-guided MMS (or slow MMS) were compared to those treated with curettage-guided MMS or “standard” MMS. Results A total of 6 studies including 508 BCCs were reviewed. There was no statistically significant difference in the proportion of total margin clearance on the first MMS stage between BCCs removed using dermoscopy-guided MMS and those that had curettage or visual inspection. However, lateral margin involvement was significantly lower in BCCs that had dermoscopy-guided MMS. Conclusions Dermoscopy allows visualization of structures up to 1mm into the dermis. Therefore, it is rational to use it for lateral margin evaluation. Currently, there are two comparative studies showing the efficacy of dermoscopy for lateral margin evaluation during MMS. Future studies are required to develop an evidence-based recommendation regarding the utility of dermoscopy in MMS.

/pdf/the-use-of-dermoscopy-in-the-delineation-of-basal-cell-rcwv75js.pdf

The Use of Dermoscopy in the Delineation of Basal Cell Carcinoma for Mohs Micrographic Surgery: a Systematic Review With Meta-Analysis

Dear Editor, Melasma is a chronic pigmentary disorder occurring commonly in women with dark skin types. It is a chronic often-relapsing condition that affects patient's quality of life. Its treatment is challenging. The use of tranexamic acid (TXA), an antifibrinolytic agent, as a treatment of melasma was first reported in 1979. Then, several studies have assessed its efficacy and safety. Oral TXA has proved to be an efficacious treatment for melasma. Side effects related to oral TXA were rarely reported and ranged from mild (gastrointestinal discomfort, skin rash, and drowsiness) to serious hypersensitivity reactions. Therefore, local infiltration with microinjections of TXA was introduced and proved to be as efficacious as oral TXA. The treatment regimen that is most commonly used is monthly intradermal microinjections of TXA 4 mg/mL at the site of melasma, keeping a distance of around 1 cm from each injection. Reported side effects are mild and include irritation, erythema, scaling, and xerosis. Hypopigmentation was reported as a side effect of oral TXA treatment but evidence of its association with intradermal TXA microinjections is lacking. We describe herein two cases. Case 1 involved a 31-year-old otherwise healthy female patient who presented with a 2-year history of centrofacial melasma. Treatment consisted of photoprotection and monthly intradermal injections of TXA (5 mg/mL) using a 0.5 mL insulin syringe. Three months after treatment initiation, a marked improvement of the Melasma Area and Severity Index (MASI) score was noted, but with no complete clearance. Due to the relapsing nature of melasma, maintenance therapy was indicated (every 6 weeks). Following the tenth session, multiple hypopigmented asymptomatic macules appeared on both arms and forearms (Figure 1). There were no scales or erythema. We decided to stop TXA microinjections. A slight repigmentation was observed after 2 months. Case 2 involved a 57-year-old woman who presented with a 7-year history of melasma. She had no relevant medical or family history, especially autoimmune disorder, thromboembolic event, miscarriage, or vitiligo. On physical examination, there were multiple brown-gray patches with irregular borders, distributed in a centrofacial pattern. Monthly intradermal injections of TXA was initiated. After 4 months, a well-demarcated depigmented macule appeared on the upper lip (Figure 2). TXA injections were stopped. After 2 months of follow-up, there was no repigmentation. We described two patterns of hypopigmentation appearing after TXA intradermal microinjections. In the first case, hypopigmented macules appeared distant to treated areas after several monthly microinjections of TXA. In this case, maintenance therapy was motivated by previous studies reporting greater recurrence rates with microinjections of TXA as compared to oral TA 250 mg twice daily, thus suggesting that intradermal TA injections should be administered frequently to achieve equivalent efficacy to oral TA. We F IGURE 1 Multiple hypopigmented asymptomatic macules on both hands and forearms

Hypopigmentation as a side effect of melasma treatment with tranexamic acid intradermal microinjections.

Dear Editor, Hydroxychloroquine (HCQ) was recently suggested for both chemoprophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data on the safety profile of HCQ in coronavirus disease-19 (COVID-19) treatment is still scarce, especially if millions of patients would be exposed to HCQ. As of April 29, 2020, the total number of confirmed COVID-19 cases exceeded 3 million. If HCQ treatment is prescribed massively for COVID-19 chemoprophylaxis and treatment, rare and severe side effects related to treatment would become more prevalent. Adverse effects of HCQ include exanthema, stomatitis, itching, and hyperpigmentation. Severe side effects encompass Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP). The latter is the most frequently reported serious side effect related to HCQ. We would like to share our experience from Tunisia. As of April 26, 2020, there are 967 accumulated COVID-19 cases. A total of 211 cases were diagnosed in Tunis. Among these cases, there was an interesting case of a 39-year-old female patient who developed AGEP after COVID-19 treatment with HCQ. She was hospitalized on March 31 for COVID-19management. The diagnosis was confirmed after nasopharyngeal swab PCR examination. She was treated with HCQ (600 mg daily), enoxaparin, and supplemental oxygen with a slight improvement of clinical signs (dry cough, dyspnea, and fever) and arterial blood gas analysis. Eighteen days after HCQ initiation, she developed a pruritic eruption. Physical examination revealed a cephalocaudal spread of erythematous and pustular plaques (Figure 1). Laboratory tests showed leukocytosis (WBC: 13 590/mm), eosinophilia (700/mm), and neutrophilia (10 355/mm). The diagnosis of AGEP was made based on clinical and histopathological examinations. Withdrawal of HCQ was indicated with significant improvement of skin lesions. Unfortunately, the patient died of a massive pulmonary embolism. COVID-19 is, indeed, associated with an increased risk of venous thromboembolism, which is responsible for significant disease-relatedmortality. AGEP is commonly attributed to antibiotics and usually occurs within 48 hours of treatment initiation. AGEP arising after HCQ treatment is distinguishable by longer incubation period (up to 2-3 weeks), cephalocaudal spread, and atypical clinical presentation including urticarial plaques, targetoid lesions, and blisters. A dilemma to which a dermatologist would be confronted is whether such cutaneous lesions are related to COVID-19 or its treatment. Reported cutaneous manifestations in COVID-19 are varied and include exanthems, purpura, urticaria, and varicella-like vesicles. Late-onset lesions are related to vasculitis or thrombotic vasculopathy. The mechanisms by which such lesions are related to SARS-CoV-2 infection remain poorly understood. We hypothesize that pustular eruptions occurring in COVID-19 patients are more likely to support drug-related origin. Given the anticipated widespread endorsement of HCQ by many governments and institutions worldwide, specific recognition of this serious side effect is vital.

Acute generalized exanthematous pustulosis after COVID-19 treatment with hydroxychloroquine.

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