"COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment".

We present the first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein. DIR to HA is reported to occur in the different scenarios including: secondary to poor injection technique, following dental cleaning procedures, following bacterial/viral illness, and after vaccination. In this report of 4 cases with distinct clinical histories and presentations: one case occured following a community acquired COVID-19 infection, one case occured in a study subject in the mRNA-1273 clinical phase III trial, one case occurred following the first dose of publically available mRNA-1273 vaccine (Moderna, Cambridge MA), and the last case occurred after the second dose of BNT162b2 vaccine (Pfizer, New York, NY). Injectable HA dermal fillers are prevalent in aesthetic medicine for facial rejuvenation. Structural modifications in the crosslinking of HA fillers have enhanced the products' resistance to enzymatic breakdown and thus increased injected product longevity, however, have also led to a rise in DIR. Previous, DIR to HA dermal fillers can present clinically as edema with symptomatic and inflammatory erythematous papules and nodules. The mechanism of action for the delayed reaction to HA fillers is unknown and is likely to be multifactorial in nature. A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II. Whereas, in the BNT162b2 case the filler reaction was suppressed with oral corticosteroids. Regarding final disposition of the cases; the vaccine-related cases returned to baseline appearance within 3 days, whereas the native COVID-19 case continued to have migratory, evanescent, periorbital edema for weeks which ultimately subsided.

Combination topical therapy for conjunctival primary acquired melanosis with atypia and periocular lentigo maligna.

PURPOSE: To report the case of a patient who initially presented with primary acquired melanosis (PAM) without atypia of the conjunctiva and later developed lentigo maligna of the eyelids and PAM with atypia of the conjunctiva. We illustrate the utility of combination topical therapy with adjunctive cryotherapy to treat extensive eyelid and conjunctival lesions. METHODS: Case report with a review of the current literature. RESULTS: Combination of imiquimod 5% cream (Aldara, 3M Pharmaceuticals) and cryotherapy for periorbital lentigo maligna with topical interferon-α2b for conjunctival PAM with atypia led to clinical resolution of pigmented lesions for 21 months. CONCLUSIONS: In our experience, combination topical therapy provides an effective alternative to surgery with superior cosmetic and functional outcomes.

Acne vulgaris: pathogenesis, treatment, and needs assessment.

Acne vulgaris is a common skin condition with substantial cutaneous and psychologic disease burden. Studies suggest that the emotional impact of acne is comparable to that experienced by patients with systemic diseases, like diabetes and epilepsy. In conjunction with the considerable personal burden experienced by patients with acne, acne vulgaris also accounts for substantial societal and health care burden. The pathogenesis and existing treatment strategies for acne are complex. This article discusses the epidemiology, pathogenesis, and treatment of acne vulgaris. The burden of disease in the United States and future directions in the management of acne are also addressed.

Clinical and cost comparisons for hysterectomy via abdominal, standard laparoscopic, vaginal and robot-assisted approaches.

INTRODUCTION: The goal of this study was to compare outcomes and costs of four methods of hysterectomy: abdominal, standard laparoscopic, vaginal and robot-assisted approaches. METHODS: We conducted a retrospective medical chart review of 1474 consecutive hysterectomy patients with benign indications. RESULTS: Implementation of a robotics program at our institution resulted in reductions in abdominal (33 percent to 8 percent) and laparoscopic (29 percent to 5 percent) hysterectomies. Robotic surgery demonstrated the least blood loss and shortest hospital stays (both p < 0.0001), despite greater case complexity. Overall complication rates were highest for abdominal procedures (14 percent) and similar across minimally invasive approaches (8 to 9 percent). Conversion rates were four times greater in laparoscopic than vaginal or robotic hysterectomy (p = 0.01). Vaginal hysterectomy, performed in the least complex cases, had the lowest major complication rate (1.5 percent) and lowest costs. Costs for robotic surgery were similar to abdominal and laparoscopic approaches when robots were not depreciated as direct surgical expenses. CONCLUSIONS: Vaginal hysterectomy was the least expensive surgical option. Robotic surgery reduced morbidity, conversions and hospital stays even in complex cases, without incurring additional costs beyond purchase of the robotic system.

First-trimester genetic diagnosis: a series of six cases.

A first-trimester screen consists of a nuchal translucency (NT) ultrasound measurement as well as maternal serum testing for pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (hCG). An increased nuchal translucency (NT) thickness at 11 to 14 weeks gestational age is a common finding for Down syndrome, Trisomy 18 and cardiac defects. We present a series of six patients, four with NT measurements greater than the 95th centile, and two additional cases where the NT was normal, but maternal serum biochemical markers were unusual. All six of these cases had a chromosome anomaly or another genetic condition: Noonan syndrome, triploidy, Down syndrome, Trisomy 18, Turner syndrome and a rare chromosome abnormality known as Ring 18-Monosomy 18. Our series underlines the fact that it is important to explore other genetic and chromosome abnormalities, in addition to Down syndrome and Trisomy 18, when there is an abnormality on a first-trimester screen.

The first-trimester screen in clinical practice.

The first-trimester screen combines nuchal translucency measurement and serum levels ot PAPP-A and beta-hCG between 11 and 13 weeks gestational age which can be used to calculate the risk of fetal Trisomy 21 and 18. Although these trisomies are the most common conditions detected, recognition of increased risk for several other fetal conditions and maternal complications have also been documented. A common misconception is that requesting this test implies that the patient will automatically terminate an affected fetus. Although termination may be one option, it is not the primary goal of this screen. If this screen results in the discovery of an abnormal fetus, the patient is allowed maximal time for privacy, formulation of a medical management plan, preparation for caring for a child with special needs, personal research and consultation with appropriate pediatric subspecialists. This test also decreases maternal anxiety throughout pregnancy. The American College of Obstetricians and Gynecologists (ACOG) recommends that all women, regardless of maternal age and risk factors, be offered this screening test. This paper addresses how the test is performed, management of abnormal findings, risk factors and detection rates.