INDIVIDUAL ARTICLE: Patient Journey and the Burden of Systemic Comorbidities and Sequalae in Prurigo Nodularis.

BACKGROUND: Prurigo Nodularis (PN) is a relatively rare chronic inflammatory skin disease characterized by firm pruritic nodules. PN is associated with significantly increased rates of many systemic and non-systemic comorbidities. This results in a higher burden of disease and utilization of specialty care compared to non-PN United States (US) adults. Psychiatric comorbidities associated with PN include depression and anxiety. In this article, we describe the burden of comorbidities. sequelae of disease, inflammatory disease signatures, and the impact of PN in African American and Asian patients. Furthermore, we explore challenges in the recognition and diagnosis of PN and describe methods to increase awareness of PN among dermatologists. J Drugs Dermatol. 2023;22:12(Suppl 2):s12-14.

A review of the current management and burden of prurigo nodularis in the United States.

Prurigo nodularis (PN) is a chronic neural- and immune-mediated disease that is characterized by intense itch, history of skin scratching, and development of papulonodular lesions. These lesions can develop consequent to a cycle of itching and scratching associated with inflammation and changes in skin cells and nerve fibers (eg, pathogenic skin fibrosis, tissue remodeling, and chronic neuronal sensitization). Diagnosis of PN involves individual evaluation of clinical characteristics to identify disease and symptom severity. In the United States, adult patients with PN (estimated, < 90,000) are more likely to be older (age, 50-60 years); in addition, this disease is detected at higher rates in women and Black individuals relative to other demographic subgroups. Still, the small population of patients with PN exhibits considerably high use of health care resources and experiences considerable symptom burden and negatively impacted quality of life. Further, PN is associated with increased rates of a range of comorbid diseases compared with other inflammatory dermatoses (eg, atopic dermatitis, psoriasis). Adequate treatment must address both the neural and immunological component of the disease; there remains a great unmet need for safe and effective therapies that can reduce the burden of disease.

Allergic Contact Dermatitis Secondary to Moisturizers.

Background: Moisturizers are cosmetic products used routinely to manage various skin conditions. Even though moisturizers are often thought to have minimal or no adverse reactions, allergic contact dermatitis (ACD) to these products can develop in some cases. Methods: We studied ingredients included in 3 of the most commonly used moisturizer brands, identified their presence in standard patch testing series, and evaluated their allergenic potential, categorizing the allergens as frequent or infrequent. The standard patch testing series used as reference were the Thin-layer Rapid Use Epicutaneous patch test (T.R.U.E. test), the North American Contact Dermatitis Group (NACDG) screening standard series, and the American Contact Dermatitis Society (ACDS) core allergen series. Results: Aveeno, Cetaphil, and Cerave products had a total of 12, 14, and 9 potential allergens, respectively, the majority of which were infrequent and not included in standard patch testing series. Conclusion: Being aware of the allergenic potential of commonly used moisturizers may help healthcare providers when evaluating patients with ACD. Further testing is recommended in a targeted manner when suspecting ACD with negative standard patch testing series or when ACD is refractory to treatment.

Pediatric Baseline Patch Test Series: Pediatric Contact Dermatitis Workgroup.

BACKGROUND: Allergic contact dermatitis is a challenging diagnostic problem in children. Although epicutaneous patch testing is the diagnostic standard for confirmation of contact sensitization, it is less used in children by dermatologists treating children, pediatric dermatologists, and pediatricians, when compared with adult practitioners. OBJECTIVE: The aim of the study was to create and evaluate standardization of a pediatric patch test series for children older than 6 years. METHODS: We surveyed dermatologists and allergists conducting epicutaneous patch testing in children attending the 2017 American Contact Dermatitis Society meeting held in Washington, DC. This was followed by discussion of collected data and consensus review by a pediatric contact dermatitis working group at the conference. CONCLUSIONS: A baseline pediatric patch test panel was established through working group consensus.

Adult Xanthogranuloma, Reticulohistiocytosis, and Rosai-Dorfman Disease.

Adult xanthogranuloma presents most commonly as an orange-tan firm solitary nodule with no systemic manifestations. Recently, some cases have been reported in conjunction with lymphoproliferative disorders. Adult reticulohistiocytosis classically presents as red to yellow-red dermal nodules. In the multicentric form, lesions have a predilection for hands and elbows, with a classic coral bead periungual presentation, and are often associated with symmetric erosive arthritis, particularly of the hands and wrists. The presentation and course of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, can vary. The classic presentation is extensive, painless bilateral cervical lymphadenopathy, but some cases have been entirely extranodal.

Written action plans: potential for improving outcomes in children with atopic dermatitis.

Asthma and atopic dermatitis are common childhood diseases requiring long-term treatment. Adherence to treatment is often poor. Written action plans (WAPs) can improve adherence in pediatric asthma. In this article we review the use of WAPs in pediatric asthma and atopic dermatitis as a basis for assessing WAPs for pediatric patients with atopic dermatitis. Results from a PubMed search for WAPs in pediatric asthma and a Cochrane review on this topic were compiled. Results from a PubMed search for education in pediatric atopic dermatitis were also reviewed. The preponderance of evidence indicates that WAPs improve adherence in pediatric asthma. No such intervention was identified for atopic dermatitis. Few controlled trials directly comparing use to non-use of a WAP were found. WAPs show promise in improving adherence in pediatric asthma, and their effect on adherence in pediatric atopic dermatitis is worthy of further investigation.

Mechanisms of AAV transduction in glaucoma-associated human trabecular meshwork cells.

BACKGROUND: Glaucoma is a chronic eye disease which leads to irreversible blindness. The trabecular meshwork tissue controls intraocular pressure (IOP), which is the major risk factor for glaucoma. Gene therapy treatment of chronic diseases requires the use of long-term expression, low toxicity and lack of immune response vectors. Adeno-associated viruses (AAV) possess these characteristics but have been unable to transduce the trabecular meshwork. Because of the importance of regulating elevated IOP by long-term gene therapy, we investigated mechanisms of AAV transduction to the human trabecular meshwork (TM). METHODS: Primary human trabecular meshwork cells (HTM) and perfused organ cultures were infected with rAAV2-GFP, RGD-pseudotyped rAAV2-GFP alone, or combined with recombinant DeltaE1/E3 adenoviruses. Intracellular rAAV2 DNA and RNA were measured by relative quantitative and real-time TaqMan polymerase chain reaction (PCR). Host transcriptome was analyzed using high-density oligonucleotide microarrays. One transduction mechanism was tested using self-complementary AAV (scAAV). RESULTS: The dramatic transduction enhancement obtained upon co-infection of rAAV2 with DeltaE1/E3 adenoviruses provides insights into transduction mechanisms in the HTM. Even if not transduced, rAAV2 enters TM cells. GeneChip analysis showed significant changes in host genes involved in cell cycle and DNA replication. Consequently, scAAV-GFP transduction was highly efficient. Other transduction-enhancement genes included coxsackie adenovirus receptor (CAR) and genes relevant to trabecular meshwork function. CONCLUSIONS: The rate-limiting step of AAV transduction was not viral entry failure but, at least in part, host downregulation of DNA replication. Additional specific host genes might be involved. Our study revealed genes and mechanisms which led for the first time to efficient AAV transduction of the HTM.

First look at the effect of overexpression of TIGR/MYOC on the transcriptome of the human trabecular meshwork.

Wild-type TIGR/MYOC is a secreted protein implicated in the development of steroid glaucoma. Mutations in TIGR/MYOC have been linked to some patients who develop elevated intraocular pressure (IOP) and glaucoma. Because there is evidence of some other factors contributing to the TIGR/MYOC causative role in glaucoma, and because substantial increased levels of a particular cellular mRNA and protein might alter expression of other host genes, we began to investigate the effect of TIGR/MYOC overexpression on the transcriptome of human trabecular meshwork cells. We used a recombinant adenovirus carrying wild-type TIGR/MYOC cDNA, primary HTM cells, 300 viral particles per cell and U133 Affymetrix GeneChips. Our results indicate that 2361 out of the 22,284 genes (10.6%) were altered more than two-fold (p