Levamisole-induced and COVID-19-induced retiform purpura: two overlapping, emerging clinical syndromes.

Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole can lead to a serious systemic syndrome known as levamisole-induced vasculitis, most commonly involving the kidneys and lungs. More recently, retiform purpura has been observed in patients with the novel coronavirus disease of 2019 (COVID-19). Due to their overlapping dermatologic and systemic manifestations, levamisole-induced and COVID-19-induced retiform purpura may mimic one another in clinical presentation. The possibility that patients may present with one or both syndromes creates a diagnostic challenge. This review of levamisole-induced and COVID-19-induced retiform purpura highlights their corresponding and distinctive features. Additionally, we propose a unique staging system for levamisole-induced retiform purpura that may be valid for future classification of COVID-19-induced retiform purpura.

Generalized Pustular Figurate Erythema in Patients with COVID-19 Treated with Hydroxychloroquine: A Systematic Review.

severe distinctive cutaneous drug reaction, generalized pustular figurate erythema, closely linked with hydroxychloroquine (HCQ), has been documented. It is distinguishable from AGEP by its longer incubation, more varied morphology (initially urticarial and later targetoid, arcuate plaques), recalcitrance to therapy and longer disease course. Aim of the article is to review the recognized entity associated with ingestion of hydroxychloroquine in patients infected with COVID-19. A systematic review using electronic search was performed. Inclusion criteria: n patients with COVID-19 demonstrated by PCR, with typical clinical features of AGEP/GPFE or atypical features associated with typical histopathology. We used the (JBI) Critical Appraisal Checklist for Case Reports for the qualitive assessment. We included 13 publications. Their overall quality was good to moderate. Only 27.3% of the patients had a severe COVID-19 course. The mean lag time between trigger exposure and rash development was 24 days. Only 15.38% of the reported AGEP were clinically typical, while the remaining 69.23 % were suggestive of GPFE. Unfortunately, 2 patients died secondary to massive pulmonary embolism. In COVID-19 infection, we suggest reconsidering treating established COVID-19 empirically with HCQ, as both triggers can augment the subsequent cytokine storm, inducing a severe drug reaction and possibly increasing the risk of thrombo-embolic events.

Pathobiology of Cutaneous Manifestations Associated with COVID-19 and Their Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a rising concern since its declaration as a pandemic by the World Health Organization on 11 March 2020. Recently, its association with multiple underlying organs has been identified that includes cardiac, renal, gastrointestinal, nervous systems, and cutaneous manifestations. Cutaneous COVID-19 findings have been supposedly classified into the following categories: vesicular (varicella-like), papulo-vesiculsar, chilblains-like ("COVID toes") maculopapular, and urticarial morphologies. In this review, we aim to focus on the proposed pathophysiology behind the various dermatological manifestations associated with COVID-19 and their associated management. We also included prevalence and clinical features of the different COVID-19-related skin lesions in our review. A comprehensive narrative review of the literature was performed in PubMed databases. Data from case reports, observational studies, case series, and reviews till June 2022 were all screened and included in the review.

Acrodermatitis continua of Hallopeau: historical perspectives and modern management.

Acrodermatitis continua of Hallopeau is a sterile pustular dermatosis primarily of the digits. Often considered a type of pustular psoriasis, it may be difficult to diagnose and even more difficult to treat. Initial involvement of a distal finger or toe may appear as erythema which should not be confused with the chilblains-like findings potentially associated with COVID-19 infection. We review the clinical manifestations of and explore potential therapeutic options for this uncommon, clinically striking dermatosis.

Leprosy: what is new.

Leprosy, also known as Hansen's disease, is an age-old chronic granulomatous infection characterized by prominent cutaneous and neurologic findings. Long known to be caused by Mycobacterium leprae, a new etiologic species was identified and linked in 2008, Mycobacterium lepromatosis. The BCG vaccine with highly variable efficacy may soon be replaced by the first leprosy-specific subunit vaccine LepVax, which has recently moved forward in human trials. Recent evidence supporting theories of zoonotic transmission from armadillos and the less-discussed Eurasian red squirrels has emerged. Knowledge on genetic polymorphisms that may increase leprosy susceptibility, such as the newly uncovered mitochondrial ribosomal protein S5 (MRPS5) polymorphism in the Chinese population, has provided a fresh perspective and direction. Further, we will delineate the latest information on leprosy, including the possible effects of leprosy coinfection with COVID-19, HIV, and HTLV-1, and the shift to newer leprosy therapies and treatment regimens.

COVID-19-specific skin changes related to SARS-CoV-2: Visualizing a monumental public health challenge.

The novel coronavirus SARS-CoV-2 has caused coronavirus disease-2019, known as COVID-19, now a pandemic stressing millions of individuals worldwide. COVID-19 is a systemic respiratory infection that may have dermatologic signs and systemic sequelae, a devastating public health challenge with parallels to the two great influenza pandemics of the last century. Skin lesions linked with COVID-19 have been grouped into six categories, with three distinct indicative patterns: vesicular (varicella-like), vasculopathic, and chilblains-like (including "COVID toes" and "COVID fingers") plus the following three less suggestive patterns: dermatitic, maculopapular, and urticarial morphologies. Vasculopathic changes are the most concerning, in some patients, reflecting a devastating blood clotting dysfunction. We discuss the ways to detect, prevent, and treat COVID-19, keeping in mind the context of possible cutaneous markers of COVID-19 to enhance detection.

Recognition and treatment of devastating vasculopathic systemic disorders: Coronavirus disease 2019 and rickettsioses.

Cutaneous involvement can be an important sign of both COVID-19 and rickettsioses. Rickettsial infections may be first evident as an exanthem with eschars as a key finding. In contrast, eschars and necrotic lesions can be seen in critically ill COVID-19 patients. Both illnesses share a similar mechanism of infecting endothelial cells resulting in vasculopathy. Rickettsia parkeri and Rickettsia 364D are both characterized by eschars unlike Rickettsia rickettsii. Other eschar causing rickettsioses such as Rickettsia conorii, Rickettsia africae, and Orientia tsutsugamushi are commonly diagnosed in people from or having traveled through endemic areas. While there is no consensus on treatment for COVID-19, rickettsioses are treatable. Due to possibly serious consequences of delayed treatment, doxycycline should be administered given an eschar-presenting patient's travel history and sufficient suspicion of vector exposure. The proliferation of COVID-19 cases has rendered it critical to differentiate between the two, both of which may have overlapping vasculopathic cutaneous findings. We review these diseases, emphasizing the importance of cutaneous involvement, while also discussing possible therapeutic interventions.

What we have learned from the COVID-19 pandemic: Time to think outside the box, maybe far outside.

The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result.

Pandemics throughout the centuries.

Pandemics have ravished the globe periodically, often associated with war, at times commencing as fever and rash, beginning in recorded history in the crowded walled city of Athens during the Peloponnesian War as described in great detail by the Athenian historian and military general Thucydides in 430 BCE. As the world now faces the first major pandemic of the 21st century, we focus on the "plague" commencing in Athens in 430 BCE and the 2 pandemics of the more recent century, which killed more than one million, the Spanish flu of 1918 and the Asian flu of 1957. The latter linked with successful vaccine development thanks to the heroic efforts of microbiologist Maurice Hilleman. We now look back and then forward to the viral infection coronavirus disease 2019 now devastating the world.

Systemic Medications of Dermatological Importance in COVID-19.

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.

Neurosyphilis and the Jarisch-Herxheimer reaction: A therapy concern with HIV disease.

Jarisch-Herxheimer reaction (JHR) should be anticipated in treating neurosyphilis with coexistent human immunodeficiency virus (HIV) encephalitis. In that context we have devised a staging classification for JHR. In addition, an illustrative case is provided to emphasize the need to consider the diagnosis of neurosyphilis in HIV patients, and if delineated, to be prepared for a severe JHR.

"Do-not-resuscitate (DNR)" status determines mortality in patients with COVID-19.

We investigatd the influence of do-not-resuscitate (DNR) status on mortality of hospital inpatients who died of COVID-19. This is a retrospective, observational cohort study of all patients admitted to two New Jersey hospitals between March 15 and May 15, 2020, who had, or developed, COVID-19 (1270 patients). Of these, 640 patients died (570 [89.1%] with and 70 [10.9%] without a DNR order at the time of admission) and 630 survived (180 [28.6%] with and 450 [71.4%] without a DNR order when admitted). Among the 120 patients without COVID-19 who died during this interval, 110 (91.7%) had a DNR order when admitted. Deceased positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients were significantly more likely to have a DNR order on admission compared with recovered positive SARS-CoV-2 patients (P < 0.05), similar to those who tested negative for SARS-CoV-2. COVID-19 DNR patients had a higher mortality compared with COVID-19 non-DNR patients (log rank P < 0.001). DNR patients had a significantly increased hazard ratio of dying (HR 2.2 [1.5-3.2], P < 0.001) compared with non-DNR patients, a finding that remained significant in the multivariate model. The risk of death from COVID-19 was significantly influenced by the patients' DNR status.

COVID-19: Topical agents and therapeutic prevention of nasal viral acquisition.

Since the spread of SARS-CoV-2 became a pandemic, the number of cases has been continuously growing worldwide. Numerous recommendations and suggestions have been published to prevent the acquisition and spread of the SARS-CoV-2, especially to protect health workers and front-line caregivers. SARS-CoV-2 is transmitted by aerosol, rendering air defense with suitable ventilation and adequate mask use pivotal. Recently, locally applied antiseptic, antiviral, or structure competitive receptor blockers were suggested to attack the virus at its main point of invasion, the nasal mucosa and nasopharynx. We discuss the most plausible and safe ideas to reduce viral load at the point of entry, and subsequently the spread of SARS-CoV-2 to the lower respiratory tract, lungs, and other organs. In addition, we analyze the value and recommend clinical trials employing topical trichloroacetic acid (TCA), a substance well known from dermatologic and cosmetic procedures. It has been proven to successfully block the nasal entry for airborne allergens, preventing the development of allergic rhinitis and asthma, and to be curative for early stages of viral infections entering through the oral mucosa. For SARS-CoV-2, TCA in a single, short-time application is expected to remodel the nasal and nasopharyngeal epithelia, eliminating both the receptors and cells responsible for viral entry and subsequent viral spread to the lower respiratory tract. Moreover, this may have therapeutic benefits for those recently infected by reducing local viral replication. Such procedures are cheap, safe, and can be conducted in almost every setting, especially in regions with inadequate financial and logistic resources.

Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration.

The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID-19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu-like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID-19 infection. There is one clinical trial initiated, the individually randomized, telemedicine-based, "Azithromycin for COVID-19 Treatment in Outpatients Nationwide" based at the University of California San Francisco. This placebo-controlled trial is designed to determine the efficacy of a single 1.2-g dose of oral azithromycin to prevent COVID-19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID-19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for 4 days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for 4 days.