The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: A retrospective chart review.

BACKGROUND: It is unclear whether the type 2 T helper cell-specific immunosuppressive action of dupilumab interferes with patch testing. OBJECTIVES: We sought to evaluate the reliability of patch testing on dupilumab and the contribution of allergic contact dermatitis (ACD) to complex dermatitis in patients with residual dermatitis on dupilumab. METHODS: This is a retrospective chart review of 48 patients with atopic dermatitis (AD) who were treated with dupilumab. We compare the results of patch tests performed before and after the initiation of dupilumab and the prevalence of comorbid ACD in patch-tested individuals. RESULTS: A minority of patch test reactions were "lost" on dupilumab (13/125; 10.4%). Five of 13 lost reactions occurred in individuals with documented immunodeficiency. Thirty-two of 35 patch-tested patients (91.4%) had comorbid ACD; 92.3% of individuals patch tested on dupilumab experienced further clinical improvement with allergen avoidance. LIMITATIONS: This is a nonrandomized study in a small cohort of patients. The clearance of dupilumab was assessed by subjective patient reports. CONCLUSIONS: Dupilumab does not appear to exert a dampening effect on patch test results. AD with comorbid ACD was highly prevalent and allergen avoidance resulted in significant improvement in residual dermatitis that had not resolved without dupilumab therapy.

The Role of Cancer Stem Cells in Recurrent and Drug-Resistant Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide with a 5-year overall survival rate of less than 20 %. Considering the treatments currently available, this statistics is shocking. A possible explanation for the disconnect between sophisticated treatments and the survival rate can be related to the post-treatment enrichment of Cancer Stem Cells (CSCs), which is one of a sub-set of drug resistant tumor cells with abilities of self-renewal, cancer initiation, and further maintenance of tumors. Lung CSCs have been associated with resistance to radiation and chemotherapeutic treatments. CSCs have also been implicated in tumor recurrence because CSCs are not typically killed after conventional therapy. Investigation of CSCs in determining their role in tumor recurrence and drug-resistance relied heavily on the use of specific markers present in CSCs, including CD133, ALDH, ABCG2, and Nanog. Yet another cell type that is also associated with increased resistance to treatment is epithelial-to-mesenchymal transition (EMT) phenotypic cells. Through the processes of EMT, epithelial cells lose their epithelial phenotype and gain mesenchymal properties, rendering EMT phenotypic cells acquire drug-resistance. In this chapter, we will further discuss the role of microRNAs (miRNAs) especially because miRNA-based therapies are becoming attractive target with respect to therapeutic resistance and CSCs. Finally, the potential role of the natural agents and synthetic derivatives of natural compounds with anti-cancer activity, e.g. curcumin, CDF, and BR-DIM is highlighted in overcoming therapeutic resistance, suggesting that the above mentioned agents could be important for better treatment of lung cancer in combination therapy.

Review of Scabies in the Elderly.

Scabies, an ectoparasitic infestation of the skin by the mite Sarcoptes scabiei, is a clinical problem of particular significance in the elderly population because of unique vulnerability factors. Such factors include reduced mobility, residency in grouped living facilities, and difficulty with implementation of certain treatments. There is also risk of transmission to nearby caretakers and cohabitants. Furthermore, the diagnosis of scabies can be difficult, as this condition can closely resemble other dermatologic diseases. Complicating the diagnosis in this group is the variety of medical settings in which these patients are evaluated, some of which may not be equipped to follow diagnostic guidelines. The diagnosis itself can be complex because of varying clinical presentation and mite burden. Finally, the transmissibility of scabies, especially in grouped living arrangements, makes prompt and proper treatment of this condition paramount. All of these factors present a unique challenge for the clinician treating elderly patients. This article aims to describe the susceptibility factors, clinical presentation, diagnosis, and management considerations specific to elderly adults with scabies.

Clinical recognition and management of alopecia in women of color.

Certain types of alopecia, such as traction alopecia, discoid lupus erythematosus, and central centrifugal cicatricial alopecia, occur more commonly in African-American individuals than in those of other ethnicities. Both intrinsic hair qualities and hair care practices play a role. Lower baseline tensile strength, hair density, and growth rates, as well as the use of high-tension hairstyles and chemical relaxers may contribute to alopecia in this group. Alopecia can also occur as a result of discoid lupus erythematosus, which involves chronic lymphocytic infiltration and eventual scarring of the hair follicle. Lichen planopilaris is a less common cause of scarring alopecia that can appear clinically similar to other forms of cicatricial alopecia. Lastly, although not classically associated with hair loss, recent evidence indicates that seborrheic dermatitis may play a role in shedding and alopecia. Recognizing and differentiating these alopecic subtypes clinically and histopathologically is important for prompt diagnosis and treatment. This article is based on a chapter in Ethnic Skin and Hair, and intended as a supplemental article to "Current and Emerging Treatment Strategies for Hair Loss in Women of Color."

Treatment of moist desquamation for patients undergoing radiotherapy.

Moist desquamation occurs in approximately 36% of patients who receive radiation therapy and is associated with severe opioid-resistant pain and discomfort. Moist desquamation is typically at its worst within 1 to 3 weeks after treatment conclusion and resolves over a period of 6 weeks. Herein, we present a therapeutic pearl for the treatment of moist desquamation based on methods from the burn literature, with the goal of helping patients who undergo radiation therapy for breast cancer and other indications.

Cutaneous endometriosis.

Cutaneous endometriosis is a disorder that primarily affects women of reproductive age. The disorder is most commonly associated with cyclical pain during menses, but it can be difficult to diagnose in the absence of these symptoms and requires biopsy testing for a definitive diagnosis. We report on a case of a 41-year-old patient undergoing hormonal therapy for infertility who presented with a painful firm subcutaneous nodule in the umbilicus. She was ultimately diagnosed with cutaneous endometriosis and underwent surgical excision. In this report, we discuss the differential diagnosis and comment on treatment options, including surgical excision with wide margins or treatment with hormonal agents, such as danazol or leuprolide. Finally, we discuss whether patients with cutaneous endometriosis should receive an additional evaluation for pelvic endometriosis.

Investigating the role of allergic contact dermatitis in residual ocular surface disease on dupilumab (ROSDD),.

BACKGROUND: The mechanisms underlying eye-related complications with dupilumab are poorly understood. OBJECTIVE: This study aimed to determine the incidence and characteristics of ocular complications with dupilumab and the prevalence of comorbid allergic contact dermatitis in the same subpopulation. METHODS: This is a retrospective chart review of 48 patients with atopic dermatitis who received dupilumab. For patients with eye involvement at first follow-up, we discuss the presence of eyelid dermatitis, blepharitis, or conjunctivitis and analyze available patch test findings in patients with ocular complications while treated with dupilumab. RESULTS: A total of 14 patients (29.2%) showed eye involvement while on dupilumab, all of whom experienced eye involvement prior to dupilumab. The results of the patch test were most commonly positive for emulsifier/surfactants (42.5%) and fragrances (30.4%). Nine patients experienced improvement with allergen avoidance subsequent to patch testing, and four of nine patients' conditions cleared almost entirely. This is a non-randomized study in a small cohort of patients. Only 18 patients had their disease confirmed by an ophthalmologist. CONCLUSION: All patients with eye involvement while on dupilumab had a history of eye involvement prior to dupilumab, suggest that dupilumab may encourage rather than cause ocular surface inflammation. Significant improvement after patch testing in nearly half of patients suggests that allergic contact dermatitis contributes to some cases of dupilumab-associated eye complications.

The Medical Necessity of Comprehensive Patch Testing.

Allergic contact dermatitis is associated with significant disease and economic burden in the United States. To properly manage allergic contact dermatitis, it is important to accurately identify the substance(s) implicated in the dermatitis to prevent disease recurrence. The commercially available T.R.U.E Test (36 allergens) screening panel has been reported to have a conservative hypothetical allergen detection rate of 66.0%, at most. Importantly, these calculations are based on the 78% of patients who had clinically relevant reactions to allergens present on the North American Contact Dermatitis Group screening series (70 allergens), without the use of supplemental allergens. Testing with supplemental allergens beyond a screening series can more fully evaluate an individual's environmental and occupational exposure, which may significantly increase diagnostic accuracy. Comprehensive patch testing with additional allergens in sunscreens, cosmetics, and fragrances, for example, may increase the diagnostic yield as well as the likelihood of achieving a cure if the dermatitis is chronic and recalcitrant.

Survey of Patch Test Business Models in the United States by the American Contact Dermatitis Society.

BACKGROUND: Allergic contact dermatitis (ACD) remains a significant burden of disease in the United States. Patch testing is the criterion standard for diagnosing ACD, but its use may be limited by reimbursement challenges. OBJECTIVE: This study aimed to assess the current rate of patch test utilization among dermatologists in academic, group, or private practice settings to understand different patch testing business models that address these reimbursement challenges. METHODS: All members of the American Contact Dermatitis Society received an online survey regarding their experiences with patch testing and reimbursement. RESULTS: A "yes" response was received from 28% of survey participants to the question, "Are you or have you been less inclined to administer patch tests or see patients needing patch tests due to challenges with receiving compensation for patch testing?" The most commonly reported barriers include inadequate insurance reimbursement and lack of departmental support. CONCLUSIONS: Compensation challenges to patch testing limit patient access to appropriate diagnosis and management of ACD. This can be addressed through a variety of innovative business models, including raising patch testing caps, negotiating relative value unit compensation, using a fixed salary model with directorship support from the hospital, and raising the percentages of collection reimbursement for physicians.

Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity.

OBJECTIVE: MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA). METHODS: First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs. RESULTS: Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-κB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRT-PCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up-regulated while miR-138 and miR-98 were down-regulated in tumors compared to normal tissues. CONCLUSION: Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies.

Contribution of microRNAs in understanding the pancreatic tumor microenvironment involving cancer associated stellate and fibroblast cells.

Understanding of molecular events associated with tumor microenvironment in pancreatic cancer (PC) is an active area of research especially because of the rich desmoplasia seen in human PC. Desmoplasia is contributed by several cell types including cancer-associated fibroblast (CAF) and stellate cells (PSCs), which are believed to play critical roles in conferring aggressiveness to PC. The aberrant expression of microRNAs (miRNAs) in PSCs and CAF cells appears to play a pivotal role in the development and progression of PC. In this study, expression analysis of miR-21/miR-221 in conditioned media derived from PSCs/CAF cells, and from PSCs/CAF cells showed up-regulation of both miRNAs compared to MIAPaCa-2 PC cells. In addition, miR-21 expression in stellate cells derived from normal pancreas was substantially lower when compared to PSCs or CAF cells. COLO-357 PC cells cultured in the presence of conditioned media derived from PSC/CAF cells led to a significant increase in clonogenicity and pancreatosphere formation. Furthermore, inhibition of miR-21 with antisense oligonucleotide (ASO) transfection resulted in decreased migration/invasive capacity of PSCs. Similarly, the effect of ASO-miR-221 transfection in CAF cells reduced the expression of NF-κB and K-Ras (target of miR-221) along with inhibition of migration/invasion. Moreover, miRNA expression profiling of PSCs, MIAPaCa-2, and COLO-357 cells, and further validation by real-time PCR, showed several differentially expressed miRNAs, among which four was significantly up-regulated. Collectively, these results suggest a crosstalk between PSCs/CAF cells and PC cells, resulting in the up-regulation of miR-21/miR-221 expression which in part may confer aggressiveness to PC. We conclude that targeting these miRNAs could be useful for developing precision medicine for the prevention of tumor progression and/or for the treatment of PC.