Characterization of Pediatric Patch Testing: A Retrospective Review, 2020-2023.

Background: Recent evidence shows similar rates of allergic contact dermatitis (ACD) among children and adults despite children accounting for less than 10% of patch testing subjects. With a need for in-depth analyses of pediatric ACD, we herein characterize a pediatric cohort at a large North American patch testing center. Methods: A retrospective chart review was conducted for 135 patients ages 1-17 years who underwent patch testing from July 2020 from August 2023. Data were stratified by age 1-5, 6-11, and 12-17 years. Significance-Prevalence Index Numbers (SPIN) were calculated. Results: A total of 86% were sensitized, 40% had a relevant reaction, and positivity rates were equal between males and females. Top allergens by SPIN differed with age, but overall were linalool hydroperoxides (SPIN = 11.01), propylene glycol (10.30), limonene hydroperoxides (10.27), fragrance mix I (5.62), and lanolin (4.90). In total, 14% of the top allergens were not represented on the North American Contact Dermatitis Group standard series. Of those tested to personal products, 45% had positive reactions and 72% of which were relevant. Conclusions: Emulsifiers and fragrances were the most relevant allergen categories, with the impact of emulsifiers not previously reported. ACD may affect males and females equally in this population. Supplemental allergens and personal products tested "as-is" contribute to conclusive pediatric patch testing.

Are "clean" products safe for children? An analysis of contact allergens in "clean" children's products from a popular retailer.

BACKGROUND: Considering consumer trends toward the use of "clean" personal care products and increasing recognition of childhood allergic contact dermatitis, we sought to characterize the allergen profile of such children's products. METHODS: Ingredients of baby washes/shampoos, bubble baths, and moisturizers identified using the "Clean Baby" filter on Target®'s online marketplace were analyzed for relevant pediatric contact allergens. RESULTS: Product compositions declared fragrance in 82% of products, Compositae in 46%, cocamidopropyl betaine in 45%, glucosides in 37%, propylene glycol in 12%, lanolin in 1%, and no allergens in 9%-methylisothiazolinone and formaldehyde were not found. CONCLUSION: Children are greatly impacted by atopic dermatitis and skin barrier dysfunction, which underscores a need for greater public awareness of sensitizing and irritating ingredients, particularly regarding pediatric personal care products.

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Allergic contact dermatitis to salicylic acid: A case series of relevant sensitization.

INTRODUCTION: Allergic contact dermatitis (ACD) to salicylic acid (SA) is widely unreported. Furthermore, cross-reactivity between SA and other salicylates has not been reported despite well-documented in-group salicylate cross-reactivity. OBJECTIVE: To describe our clinic's experience patch testing to SA, highlighting seven cases of relevant reactions and concomitant reactivity with other salicylates. METHODS: Results of patch testing to 5% SA in petrolatum between 1 January 2020, and 9 February 2024, are reported. Seven cases of relevant reactions to SA are detailed. RESULTS: A total of 489 patients (27.5%) were tested to SA, 21 of which were positive: 7 doubtful (+/-), 14 weak positive (+), and no strong/extreme positive reactions. Four irritant reactions were documented. Of the 14 weak positive (+) reactions, 7 had definite or probable clinical relevance, 5 of which also reacted to other salicylates. CONCLUSIONS: ACD to SA is likely underreported due to a lack of testing. In our experience, testing SA 5% petrolatum is tolerable without significant irritation. Cross-reactivity between SA and other salicylates is probable. Though SA appears to be the primary sensitizer in some cases, more studies are needed to understand its possible role as a marker for salicylate allergy.

Effects of Quinidine or Rifampin Co-administration on the Single-Dose Pharmacokinetics and Safety of Rilzabrutinib (PRN1008) in Healthy Participants.

This open-label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug-drug interaction between rilzabrutinib and quinidine (an inhibitor of P-glycoprotein [P-gp] and CYP2D6) or rifampin (an inducer of CYP3A and P-gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash-out period, after co-administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0-∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P-gp.

Efficacy and Safety of Rilzabrutinib in Pemphigus: PEGASUS Phase 3 Randomized Study.

TRIAL DESIGN: Pemphigus is a rare but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety. METHODS: Adults (aged 18-80 years) were randomized 1:1 to 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily (with CS ≤ 0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/pemphigus foliaceus. RESULTS: The primary endpoint of complete remission from week 29 to week 37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13 of 54 (24%) rilzabrutinib versus 10 of 55 (18%) placebo patients with PV (P = .45). Secondary endpoints showed numerical but nonsignificant improvements with rilzabrutinib (vs placebo) in reduced CS use, prolonged complete remission duration, and faster time to first complete remission. CONCLUSIONS: Overall, rilzabrutinib was well-tolerated, with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support Bruton tyrosine kinase inhibition as a viable therapeutic approach for pemphigus.

Clinical relevance of doubtful reactions in patch testing: A single-centre retrospective study.

BACKGROUND: Doubtful reactions in patch testing are infrequently reported in the literature; however, recent reports have suggested they be assessed with the same scrutiny as stronger reactions. OBJECTIVE: Assess the clinical relevance of doubtful reactions in patch testing. METHODS: Retrospective study of 1514 patients comprehensively patch tested via the NACDG standard series and additional allergens based on history. The clinical relevance of each reaction was graded based on the NACDG scale: definite, probable, possible, past, unknown and irritant. Reactions were considered 'unique' if an additional mild-to-strong reaction to the same chemical at a different concentration was not observed. RESULTS: 68.9% (1043) of patients demonstrated at least 1 doubtful reaction. Of 4453 total doubtful reactions, 92.2% (4106) were unique. Only 3.3% (137) and 12.2% (500) of these were determined to be of definite or probable clinical relevance respectively. 'Fragrance' was the most common allergen family present among the unique definite doubtful reactions (37). However, 24 (64.9%) of these also had a stronger reaction to another fragrance. Cocamidopropyl betaine was the second most frequent allergen demonstrating definite doubtful reactions (27) and unique in 85.2% (23) of cases. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was most prevalent (36) but less frequently unique (58.3%, 21). CONCLUSIONS: Doubtful reactions may not be as impactful to clinical decision making as theorised in the literature. Few demonstrate definite clinical significance, and many have related stronger reactions that capture them for clinical purposes. Identification of doubtful reactions to cocamidopropyl betaine and MCI/MI may be of greatest significance as they most frequently were not supported by stronger reactions.

Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India.

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

The Diagnostic Value of Delayed-Type Reactions to Perennial Aeroallergens for Atopic Disease.

Background: Delayed-type reactions to aeroallergens have been observed, however, their clinical significance continues to be debated. Objective: We assessed the prevalence and significance of delayed-type reactions to aeroallergens in atopic patients. Methods: Retrospective study including 266 patients with history or evidence of atopic disease (atopic dermatitis [AD], allergic rhinitis, and/or allergic asthma) and tested via either the intradermal skin test (IDT) or atopy patch test for common aeroallergens, specifically house dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and perennial molds (Aspergillus fumigatus, Penicillium notatum). All patients were tested via IDT with both immediate (15 minute) and delayed (2 and 4 days) readings. Delayed reading was considered positive if the IDT injection site demonstrated at least 5 mm induration 48 hours after inoculation. Results: In total, 195 (73.3%) patients demonstrated an immediate-type reaction, whereas 118 (44.4%) had a delayed-type reaction. In total, 75 (28.2%) patients experienced both immediate- and delayed-type reactions, 43 (16.2%) reacted delayed-type only, and 85.3% of delayed-type reactions to individual aeroallergens were associated with eczematous lesions predominantly in air-exposed areas. Conclusion: Delayed-type reactions to aeroallergens are prevalent and clinically significant as a component of extrinsic AD and atopic diseases. The data support delayed reading of the IDT to guide diagnosis and management in these patients.

A Comparative Analysis of Chikungunya in Kidney Transplant Recipients Compared With the General Population: A Multicenter, Retrospective, Cohort Study From India.

OBJECTIVES: Chikungunya is an arboviral illness, with patients presenting with fever, arthralgias, and myalgias. Outbreaks have occurred in tropical regions, and the virus is now endemic to many tropics, including South Asia, with India contributing a large part of the global burden. The presentation and long-term effects on transplant recipients are largely unknown. MATERIALS AND METHODS: In this retrospective analytical study, we compared chikungunya infection in 44 kidney transplant recipients from multiple centers in India and 34 patients from the general population. Data were collected from medical records and patient recall. RESULTS: Differences in presentation were remarkable between the 2 groups, with significantly lower incidence of musculoskeletal symptoms on presentation in transplant recipients compared with the general population. The incidence of acute graft dysfunction was 17.08% in transplant recipients, with return to baseline at the end of 1 month. Acute symptomatology resolved in transplant recipients within 1 month, and insignificant chronic symptoms were reported after 3 months. CONCLUSIONS: Chikungunya in kidney transplant recipients is markedly different from that of the general population, with significantly lower incidence of musculoskeletal symptoms such as arthralgias. The infection caused acute graft dysfunction, but no long-term sequelae were shown at the end of 1 year.

Honey flower dermatitis: Contact allergy to ellagic acid in Melianthuscomosus.

A case study is reported whereby a patient with no prior allergies developed a strong and spreading delayed-type hypersensitivity reaction to Melianthus plants, nectar and synthetic pigment derived from it after frequent handling of these substances. The lesions improved after treatment with topical steroids and allergen avoidance within 1-2 weeks. Subsequent patch testing with the plants, nectar and synthetic ingredients identified ellagic acid (EA) as the sensitizing agent. This is the first proven case of allergic contact dermatitis to EA, a phenolic substance present in numerous plants, fruits, and nuts regularly consumed by humans. Melianthus use is growing worldwide as an ornamental plant. Moreover, it is used in traditional South African medicine for its anti-inflammatory effects. In recent years, these extracts and EA have been added to natural, plant-based topical formulations for the treatment of inflammatory skin disorders. Our observation that the EA found in Melianthus can induce severe contact allergy should caution for the possible dangers of specific allergic sensitizations to these increasingly used additives in natural medicines.

Developmental Potential of embryos does not Impact Pregnancy Outcomes, but it Affects Live Birth Rates in Frozen Blastocyst Transfer Cycles.

OBJECTIVE: This study aimed to determine whether or not developmental potential impacts clinical outcomes, when good grade blastocysts from Days 5 and 6 were transferred in frozen embryo transfer (FET) cycles. METHODS: 654 women, including 460 (70.33%) on Day 5 and 194 (29.66%) on Day 6 were analyzed, in which 905 Day-5 and 274 Day-6 blastocysts were transferred. Only grade AA, AB, BA, BB quality and expansion grade between 3-6 (Gardner grading system) blastocysts survived and were included. RESULTS: The implantation rate was higher, 41.9% (379/905) in normal Day-5 compared to delayed Day-6 blastocyst transfers - 36.5% (100/274), but not significant (p=0.1). The clinical pregnancy rate was similar and not significant (p=0.4) in normal Day-5 (32.4%), compared to delayed Day-6 (35%). Miscarriage rates were higher in normal Day-5 (13.3%) compared to delayed Day-6 (6.3%) blastocyst transfers but were not significant (p=0.06). On the other hand, the biochemical pregnancy rate was significantly higher (p=0.001) in the delayed Day-6 blastocysts (16.7%) transfer group compared to patients with normal Day-5 (2.4%) blastocyst transfers. Two patients had ectopic pregnancies from the delayed Day-6 blastocyst transfer group. Live-Birth rates were significantly higher in Day-5 blastocysts compared to Day-6 (p=0.03). CONCLUSIONS: The developmental potential of embryos should not be considered a negative influence on pregnancy outcomes, especially good grade blastocysts vitrified on Days 5 and 6. Fully expanded blastocysts on Day-5 are considered similar in terms of outcomes to delayed Day-6 blastocysts; however, live-birth rates are significantly higher in Day-5 blastocysts.

Late Preterm Infant With Postnatal Diagnosis of Renal Tubular Dysgenesis.

A male infant born at 34 weeks' gestation presented with acute cardiorespiratory decompensation soon after birth followed by renal failure. Initial clinical course was complicated by ventilator requirement, bilateral pneumothoraces, and hypotension managed with multiple inotropes. Persistent renal failure with oliguria and renal ultrasound showing noncystic medical renal disease prompted further investigation. Whole-exome sequencing showed 2 pathologic mutations in the angiotensin-converting enzyme (ACE) gene, suggesting a diagnosis of renal tubular dysgenesis (RTD). Renal tubular dysgenesis is usually a fatal condition affecting the renin-angiotensin system with possible autosomal recessive inheritance. Acquired cases have been described in the setting of in utero exposure to medications such as nonsteroidal anti-inflammatory medications (NSAIDs) and ACE inhibitors. Renal tubular dysgenesis should be suspected in any neonate presenting with renal failure, refractory hypotension, ventilator requirement, hypoplastic lungs, renal ultrasound showing normal-sized echogenic noncystic kidneys with poor corticomedullary differentiation, and antenatal history significant for oligohydramnios. The overall prognosis of patients with RTD continues to improve with better ventilatory management and renal replacement therapies.