Stephanie D. Gan

Enzyme Immunoassay and Enzyme-Linked Immunosorbent Assay

inTrOducTiOn Enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA) are both widely used as diagnostic tools in medicine and as quality control measures in various industries; they are also used as analytical tools in biomedical research for the detection and quantification of specific antigens or antibodies in a given sample. These two procedures share similar basic principles and are derived from the radioimmunoassay (RIA). RIA was first described by Berson and Yalow (Yalow and Berson, 1960), for which Yalow was awarded the Nobel Prize in 1977, to measure endogenous plasma insulin. RIA was then developed into a novel technique to detect and measure biological molecules present in very small quantities, paving the way for the analysis and detection of countless other biological molecules, including hormones, peptides, and proteins. Because of the safety concern regarding its use of radioactivity, RIA assays were modified by replacing the radioisotope with an enzyme, thus creating the modern-day EIA and ELISA.

Intracellular Degradation of Elastin by Cathepsin K in Skin Fibroblasts— A Possible Role in Photoaging

Solar elastosis is observed in the dermis of photoaged skin and is characterized by an accumulation of abnormal elastin in the extracellular space. Several proteases that degrade elastin in the extracellular space have been implicated in its formation. The lysosomal protease cathepsin K (catK) has recently been described to be highly expressed in skin fibroblasts under certain pathologic conditions. As cat K is one of the most potent mammalian elastases, we hypothesized that catK‐mediated intracellular elastin degradation may play a role in the formation of solar elastosis. Immunostaining of cultured skin fibroblasts incubated with labeled elastin demonstrated internalization of extracellular elastin to lysosomes and its degradation by catK. Induction of catK expression in fibroblasts was observed both in vitro and in vivo after exposure to longwave UVA. In contrast to fibroblasts from young donors, cells from old donors failed to activate catK in response to UVA. These data suggest a role of intracellular elastin degradation by catK in the formation of solar elastosis. We propose that an age‐related decline in catK activity, in particular after UV exposure, may promote the formation of actinic elastosis through a decline of orderly intracellular elastin degradation and subsequent accumulation of elastin in the extracellular space.

A Critical Evaluation of Clinical Research Study Designs

Interventional and observational studies have important roles in dermatology. The results from any study must be put in the context of the appropriate research design selection. RCTs are most useful in determining causality and effectiveness of treatment. Observational studies provide information about epidemiology and possible links between exposure and disease. Understanding the fundamentals underlying the various study designs is critical to both investigators and clinicians alike.

Ablative Fractional Laser-Assisted Topical Fluorouracil for the Treatment of Superficial Basal Cell Carcinoma and Squamous Cell Carcinoma In Situ: A Follow-Up Study.

BACKGROUND The authors previously reported the safety and short-term efficacy of ablative fractional laser (AFXL)–assisted delivery of topical fluorouracil in the treatment of superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). OBJECTIVE This follow-up study was conducted to assess whether tumor clearance was sustained in this cohort of patients at >9 months post-treatment. METHODS Thirty primary sBCC or SCCis <2 cm on the trunk or extremities were treated with AFXL and a single application of topical 5-fluorouracil 5% under occlusion for 7 days. Among the 26 patients who achieved tumor clearance at 4 to 8 weeks post-treatment, 20 patients presented for this follow-up study and underwent shave biopsy to confirm histologic clearance. Mean follow-up time was 15 months. RESULTS Considering those who had persistent tumor at 4 to 8 weeks post-treatment and those who presented for follow-up at >9 months post-treatment, overall treatment success was 79% (95% confidence interval: 67%–96%), with 92% (11/12) for SCCis and 67% (8/12) for sBCC. Neither the tumor location nor size significantly impacted treatment outcome (p = .96 and 0.87, respectively). CONCLUSION Ablative fractional laser–assisted topical fluorouracil is a reasonable noninvasive treatment option for primary SCCis and sBCC, especially for lesions located in areas where self-application is not possible, or when clinician-administered therapy is preferred.

Ablative fractional laser therapy for the treatment of actinic keratosis: A split-face study

REFERENCES 1. Wu XC, Eide MJ, King J, et al. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006. J Am Acad Dermatol. 2011;65:S26-S37. 2. Hu S, Sherman R, Arheart K, Kirsner RS. Predictors of neighborhood risk for late-stage melanoma: addressing disparities through spatial analysis and area-based measures. J Invest Dermatol. 2014;134:937-945. 3. Ma F, Collado-Mesa F, Hu S, Kirsner RS. Skin cancer awareness and sun protection behaviors in white Hispanic and white non-Hispanic high school students in Miami, Florida. Arch Dermatol. 2007;143:983-988. 4. Dobbinson S, Wakefield M, Hill D, et al. Children’s sun exposure and sun protection: prevalence in Australia and related parental factors. J Am Acad Dermatol. 2012;66:938-947. 5. Rouhani P, Parmet Y, Bessell AG, Peay T, Weiss A, Kirsner RS. Knowledge, attitudes, and behaviors of elementary school students regarding sun exposure and skin cancer. Pediatr Dermatol. 2009;26:529-535.

Hemosiderin hyperpigmentation: Successful treatment with Q-switched 755-nm laser therapy

Hyperpigmentation due to iron or, more commonly, hemosiderin deposition is a disfiguring condition that is often recalcitrant to therapy. Previous reports have noted improvement with theQ-switched (QS) 650-nm laser used to treat hyperpigmentation secondary to hemosiderin and melanin from necrobiosis xanthogranuloma and the QS 694-nm ruby laser for treating postsclerotherapy hemosiderin-induced hyperpigmentation. The authors report a case of iron deposition effectively treated with the QS 755-nm Alexandrite laser.

Facial Erosive Pustular Dermatosis After Cosmetic Resurfacing

Importance Erosive pustular dermatosis (EPD) is a rare condition that typically affects actinically damaged skin of the scalp. Characterized by sterile pustules, erosions, and crusts, EPD is difficult to treat and heals slowly. The exact cause of EPD is unknown, although trauma is an inciting factor. Objective To describe 3 women who presented with prolonged facial erosions after cosmetic resurfacing procedures, specifically fully ablative carbon dioxide laser or medium-depth chemical peel. Design, Setting, and Participants This case series describes the clinical features, histopathological findings, laboratory results, and treatment of 3 patients with an ultimate diagnosis most consistent with facial EPD. Patients were evaluated between September 10, 2010, and May 6, 2016, in a dermatology clinic in an academic medical center. The patients were 3 women seeking diagnostic evaluation and therapeutic options for nonhealing facial erosions occurring after ablative procedures (carbon dioxide laser resurfacing or Jessner solution/trichloroacetic acid chemical peel). Main Outcomes and Measures Histologic examination and wound culture from initial presentation as well as clinical follow-up documenting improvement with therapeutic interventions. Results All 3 patients were women in their 50s or 60s for whom EPD was deemed to be the best diagnosis, after infection, immunobullous disorders, and other pustular dermatoses were considered. Histologic features were nonspecific. Treatment included a combination of topical and systemic therapies, such as corticosteroids, dapsone, isotretinoin, and/or antibiotics. Watchful waiting (tincture of time) appeared to be central to the healing process. Conclusions and Relevance After cosmetic resurfacing, patients may develop EPD isolated to the face. As a diagnosis of exclusion that should be considered in patients who have nonhealing wounds following ablative procedures, EPD is challenging to treat and may require the use of anti-inflammatory agents. Recognizing this condition is important, especially as cosmetic procedures become more widespread.

Nonablative Fractional Resurfacing for the Treatment of Iatrogenic Hypopigmentation

Hyaluronic acid fillers are extremely popular because of their favorable safety profile and potential for dissolution with hyaluronidase. Because of the natural thinness of the skin below the eye, placement of filler in the tear trough should be deep, below the orbicularis oculi just above the bone. An experienced physician (NL) injected all of our patients, and product was placed deep to the orbicularis oculi muscle with a 30-G needle inferior to the orbital bone and massaged into proper position. No patients had a history of eyelid surgery, although patients 1 and 3 had had periorbital botulinum toxin injections intermittently. To the best of our knowledge, this is the first published case report of hyaluronic acid causing a delayed Tyndall effect due to migration of product superficially, years after implantation.

Hyaluronic acid-induced alopecia: a novel complication.

Well-known complications of filler injections include pain, dyspigmentation, bruising, and rarely, iatrogenic blindness. Localized alopecia secondary to hyaluronic acid injections is a previously unreported complication of fillers. The clinical features and histologic evidence indicate vascular compromise as the etiology of filler-induced alopecia. Awareness of vascular occlusion as the cause of these complications affords appropriate targeted therapy.

Fever and a Solitary Papule on the Foot

A woman in her 30s presented to a tertiary care Boston hospital with a 5-day history of fevers, malaise, headaches, and nausea with a concurrent asymptomatic solitary papule on her right foot. At the time, she was living in a house infested with mice but did not recall any rodent or insect bite. Physical examination revealed a round dusky papule 5 mm in diameter with surrounding erythema on the dorsal aspect of the right foot (Figure, A). No other cutaneous lesions or regional lymphadenopathy were identified. All laboratory tests had normal results except for an elevated monocyte count. Two sterile punch biopsy specimens were sent for culture and histopathologic examination, respectively. Routine hematoxylin-eosin–stained sections are shown in Figure, B and C. What is your diagnosis?