Updates on postinfectious skin rashes in pediatric dermatology.

PURPOSE OF REVIEW: This review provides updates on postinfectious skin rashes in the pediatric population from recently published literature. RECENT FINDINGS: The COVID-19 pandemic and its sequelae remain a focus of research on pediatric infectious skin rashes. Multisystem inflammatory syndrome in children (MIS-C) and reactive infectious mucocutaneous eruption (RIME) are common complications of infection with SARS-COV-2 in the pediatric population. Most cases of MIS-C show low mortality and suggest mucocutaneous symptoms do not correlate with COVID-19 disease severity. Cases of papular acrodermatitis of childhood, also known as Gianotti-Crosti, have also been reported in association with SARS-COV-2, and can present similarly in reaction to other viral infection like molluscum contagiosum, known as a Gianotti-Crosti syndrome-like reaction (GCLR). Other relevant studies on postinfectious skin rashes include updates on the management of staphylococcal scalded skin syndrome (SSSS), with newer evidence advocating for beta-lactam monotherapy without clindamycin and reduced ancillary testing. Finally, the emergence of antifungal resistance due to Trichophyton indotinae is a growing global health concern emphasizing the need for improved antifungal stewardship. SUMMARY: It is prudent for clinicians to be informed of both common and rare diagnoses that have emerged more recently in association with the COVID-19 pandemic, in addition to other diseases with newer evidence-based recommendations to guide management.

Localized calcium oxalate crystals in primary cutaneous aspergillosis.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.

SCALP syndrome with a germline heterozygous DOCK6 mutation and somatic mosaic NRAS Q61R mutation.

We present a case of SCALP syndrome, which was diagnosed in a male infant with the characteristic findings of sebaceous nevi, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and giant congenital melanocytic nevi, or pigmented nevi. We identified a germline compound heterozygous DOCK6 mutation and a somatic mosaic NRAS Q61R mutation in the giant congenital melanocytic nevus. This report will increase clinician awareness of SCALP syndrome and augment the literature in characterizing this rare syndrome, including its genetic background.

Treatment of pediatric alopecia areata: A systematic review.

BACKGROUND: Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking. OBJECTIVE: To evaluate the evidence of current treatment modalities for pediatric AA. METHODS: We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available. RESULTS: Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab. LIMITATIONS: English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed. CONCLUSION: Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.

Anogenital warts and relationship to child sexual abuse: Systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: In children, distinguishing anogenital warts (AGW) acquired innocently from those acquired by child sexual abuse (CSA) is challenging. High-quality studies examining this relationship are sparse. Here, we sought to evaluate the association between AGW and sexual abuse in children 12 years of age and younger with respect to wart location, age, and gender. METHODS: A systematic review of Ovid MEDLINE, Embase, and Web of Science was performed for studies published on or before 2/16/2018. Studies were eligible for inclusion if they contained at least 10 patients 12 years old and younger and reported the number of patients who were sexually abused. The principal summary measures were the odds ratios (OR) of reported CSA with respect to subject age, wart location, and gender. RESULTS: Three hundred twenty-seven studies were identified through record search. Twenty five were included in a summary synthesis (791 subjects); 10 were included in the final statistical analysis (199 subjects). In our overall review, 102 of 468 (21%) females and 36 of 204 (18%) males with AGW were abused or probably abused. Overlapping HPV types were found in abused and non-abused subjects. Perianal location and gender were not significant predictors of abuse. Both age and genital wart location (penis, vulva) did significantly predict CSA (α = .05). The odds ratio for sexual abuse of children aged 3-4 years was 7.45; 6.52 for ages 5-8 years; and 6.93 for ages 9-12 years compared to those 0-2 years of age. Genital location was associated with an OR of CSA of 5.93. CONCLUSIONS: Our systematic review supports a significant association between AGW in a child greater than 2 years of age and odds of CSA. Genital wart location significantly predicts CSA as well. HPV typing is not a reliable method to ascertain CSA. Male family members and acquaintances were the most likely perpetrators of abuse.

Nevoid Basal Cell Carcinoma Syndrome and Hairy Skin Patches.

We report a case of an increasing number of discrete patches of darkly pigmented terminal hair in a patient with nevoid basal cell carcinoma syndrome. This case adds to a small case series of three patients which have previously reported this observation. We report this case to highlight hairy patches as an important clinical feature associated with nevoid basal cell carcinoma syndrome.

A Report of Two Patients with Darier Disease and Hidradenitis Suppurativa.

We report two unique cases of patients with Darier disease and hidradenitis suppurativa. Although it is unknown whether there is a connection between the two diseases, it is possible that an interaction between sarcoendoplasmic reticulum calcium transport ATPase and Notch homolog 1, translocation-associated (Drosophila) caused both diseases in these individuals.

The ErbB3-binding protein EBP1 modulates lapatinib sensitivity in prostate cancer cells.

Although ErbB receptors have been implicated in prostate cancer progression, ErbB-directed drugs have not proven effective for prostate cancer treatment. The ErbB3-binding protein EBP1 affects both ErbB2 and androgen receptor signaling, two components of the response to ErbB-targeted therapies. We therefore examined the effects of EBP1 expression on the response to the ErbB1/2 tyrosine kinase inhibitor lapatinib. We found a negative correlation between endogenous EBP1 levels and lapatinib sensitivity in prostate cancer cell lines. We then overexpressed or inhibited expression of EBP1. Silencing EBP1 expression increased lapatinib sensitivity and overexpression of EBP1 increased resistance in androgen-containing media. Androgen depletion resulted in an increased sensitivity of androgen-dependent EBP1 expressing cells to lapatinib, but did not affect the lapatinib sensitivity of hormone resistant cells. However, EBP1 silenced cells were still more sensitive to lapatinib than EBP1-expressing cells in the absence of androgens. The increase in sensitivity to lapatinib following EBP1 silencing was associated with increased ErbB2 levels. In addition, lapatinib treatment increased ErbB2 levels in sensitive cells that express low levels of EBP1, but decreased ErbB2 levels in resistant EBP1-expressing cells. In contrast, ErbB3 and phospho ErbB3 levels were not affected by either changes in EBP1 levels or lapatinib treatment. The production of the ErbB3/4 ligand heregulin was increased in EBP1-silenced cells. EBP1-induced changes in AR levels were not associated with changes in lapatinib sensitivity. These studies suggest that the ability of EBP1 to activate ErbB2 signaling pathways results in increased lapatinib sensitivity.

Set-back versus buried vertical mattress suturing: results of a randomized blinded trial.

BACKGROUND: The set-back suture, an absorbable dermal suturing technique, purportedly improves wound eversion and cosmetic outcomes. OBJECTIVE: We sought to conduct a split-wound, prospective, randomized study to compare the cosmetic outcome and wound eversion achieved with the set-back suture and the buried vertical mattress suture (BVMS). METHODS: A total of 46 surgical elliptical wounds were randomized to subcuticular closure with the set-back suture on half and the BVMS on the other. Maximum eversion height and width were measured immediately postoperatively. At 3 months, 2 blinded observers evaluated each scar using a 7-point Likert physician global scar assessment scale. Subjects and observers also completed the validated Patient and Observer Scar Assessment Scale, where a score of 6 represents normal-appearing skin and 60 represents worst imaginable scar. RESULTS: In all, 42 subjects completed the study. The set-back suture provided statistically significant wound eversion. On the Likert scale, observers rated the set-back suture side 1 point better than the BVMS side. Both patient and observer total Patient and Observer Scar Assessment Scale scores were significantly lower for the set-back suture side (subject mean 13.0 ± 8.7 vs 16.2 ± 12.0 [P = .039]; observer mean 24.5 ± 10.4 vs 27.7 ± 13.6 [P = .028], respectively). LIMITATIONS: Single institution experience and relatively short follow-up are limitations. CONCLUSION: The set-back suture provides superior wound eversion and better cosmetic outcomes than the BVMS.

Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility.

TTLL5/STAMP (tubulin tyrosine ligase-like family member 5) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamp(tm/tm)) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamp(tm/tm) sperm tails in conjunction with substantial reduction in α-tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of WT versus Stamp(tm/tm) males despite the levels of WT STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for α-tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility.

Heregulin negatively regulates transcription of ErbB2/3 receptors via an AKT-mediated pathway.

Despite the importance of the ErbB2/3 heterodimer in breast cancer progression, the negative regulation of these receptors is still poorly understood. We demonstrate here for the first time that the ErbB3/4 ligand heregulin (HRG) reduced both ErbB2 and ErbB3 mRNA and protein levels in human breast cancer cell lines. In contrast, EGFR levels were unaffected by HRG treatment. The effect was rapid with a decline in steady-state mRNA levels first noted 2 h after HRG treatment. HRG reduced the rate of transcription of ErbB2 and ErbB3 mRNA, but did not affect ErbB2 or ErbB3 mRNA stability. To test if ErbB2 kinase activity was required for the HRG-induced downregulation, we treated cells with the ErbB2/EGFR inhibitor lapatinib. Lapatinib diminished the HRG-induced decrease in ErbB2 and ErbB3 mRNA and protein, suggesting that the kinase activity of EGFR/ErbB2 is involved in the HRG-induced receptor downregulation. Further, HRG-mediated decreases in ErbB2/3 mRNA transcription are reversed by inhibiting the AKT but not MAPK pathway. To examine the functional consequences of HRG-mediated decreases in ErbB receptor levels, we performed cell-cycle analysis. HRG blocked cell-cycle progression and lapatinib reversed this block. Our findings support a role for HRG in the negative regulation of ErbB expression and suggest that inhibition of ErbB2/3 signaling by ErbB2 directed therapies may interfere with this process. J. Cell. Physiol. 229: 1831-1841, 2014. © 2014 Wiley Periodicals, Inc.

Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations.

Control of gene transcription by glucocorticoid receptors (GRs) is important for many physiological processes. Like other steroid hormone receptors, the regulation of target genes by GR is mediated by two transactivation domains: activation function 1 (AF1) in the N-terminal domain and AF2 in the C-terminal ligand-binding domain (LBD). Full receptor activity requires both AF1 and -2 plus assorted coregulatory proteins. Crystal structures of the ligand-bound LBD have provided insight regarding how AF2 interacts with specific coactivators. However, despite its being the major activation domain of GRs, knowledge of AF1 structure/function has languished. This is mainly because of the highly disorganized structure of the GR N-terminal domain. This lack of AF1 structure is shared by all members of the steroid/nuclear receptor superfamily for which it has been examined and AF1 is thought to allow productive interactions with assorted cofactors via protein-induced changes in secondary/tertiary structures. To date, there are no reports of a classical coactivator altering the secondary/tertiary structure of the GR AF1 domain. Earlier, we reported an N-terminal fragment of the p160 coactivator TIF2, called TIF2.0, that binds the GR N-terminal domain and alters GR transcriptional activity. We therefore proposed that TIF2.0 binding to AF1 changes both its conformation and transcriptional activity. We now report that TIF2.0 interacts with the GR AF1 domain to increase the amount of α-helical structure in the complex. Furthermore, TIF2 coactivator activity is observed in the absence of the GR LBD in a manner that requires the AF1 domain. This contrasts with previous models where TIF2 receptor interaction domains binding to GR LBD somehow alter AF1 conformation. Our results establish for the first time that coactivators can modify the structure of the AF1 domain directly via the binding of a second region of the coactivator and suggest a molecular explanation for how coactivators increase the transcriptional activity of GR-agonist complexes.

Sebaceous nevus syndrome: a case report of a child with nevus sebaceus, mental retardation, seizures, and mucosal and ocular abnormalities.

A 12-year-old girl presented with extensive epidermal nevi, new onset seizures, mental retardation, and oral and ocular abnormalities. We briefly review the case and epidermal nevus syndrome (ENS), which is characterized by epidermal nevi occurring in conjunction with neurologic, ocular, skeletal, and/or other system involvement.

The Use of Prompts and Precision Teaching to Address Speech Sound Disorders in a 17-Year-Old Girl With Autism.

Precision teaching is a measurement system that uses frequency as its basic data and plots those data on a standard celeration chart for practitioners to make decisions (Maloney, 1998). Kay, a 17-year-old girl with autism spectrum disorder and profound speech sound disorder, participated in this multiple-baseline across-behaviors study. The syllables "thu," "fu," and "cu" were targeted for higher frequencies of correct echoic responding in isolation. Lip-tongue-teeth position prompts, frequency building (Fabrizio & Moors, 2003, European Journal of Behavior Analysis, 4(1-2), 23-36), and feedback were used in brief timed practice trials for the first 2 skills. Priming (Cihon et al., 2017) was also added to the third syllable. The frequency of correct responses accelerated from low levels in baseline to a frequency aim of 60 per minute or higher, with intervention for all 3 targets. The accuracy of her articulation with 30 functional words with the component consonant sounds was measured and showed significant improvements from baseline to postintervention. The outcomes representing fluent performance were also achieved. The implications of training for fluency of syllables on word speech are discussed.

Transitioning ABA Services From in Clinic to Telehealth: Case Study of an Indian Organization's Response to COVID-19 Lockdown.

Due to the coronavirus (COVID-19) pandemic, around the middle of March 2020, in-clinic intervention services based in applied behavior analysis provided to children had to be stopped abruptly in India. This qualitative and quantitative case study details how Behavior Momentum India (BMI), an organisation providing ABA-based interventions, transitioned services from in clinic to telehealth while continuing to target each student's skill acquisition goals in language and communication domains. A cohort of 92 students diagnosed with autism or other learning disabilities participated in this study; 51 therapists, 9 behavior supervisors, and a doctoral-level Board Certified Behavior Analyst collaborated with parents; 78% of the students and 82% of the therapists used smartphones; and only a few used iPads and laptops. Therapists conducted direct sessions and parent-mediated sessions with 82 students. With 10 students, behavior supervisors trained parents to implement interventions with their children. The critical transition decisions, logistics, and ethical challenges were identified using qualitative methods. Despite significantly reduced session durations, all students continued to acquire targeted skills, and 52% of the students acquired more skills in telehealth compared to in clinic. A parent satisfaction survey returned high ratings onour organization's initiative, and 72% of the parents reported that their familiarity and confidence with the science of applied behavior analysis had increased.

Behavioral Interventions to Treat Speech Sound Disorders in Children With Autism.

Children with autism are at a higher risk of being affected by speech disorders and often require remedial intervention. Eikeseth and Nesset (Journal of Applied Behavior Analysis, 36(3), 325-337, 2003) used sufficient-response exemplar training of vocal imitation in conjunction with prompting, chaining, and shaping procedures to successfully teach 2 typically developing children to articulate several Norwegian words with blends. The present study extends and adapts these procedures to children with autism. Participants were TA, an 11-year-old boy, and KS, a 15-year-old girl, both with autism and speech sound disorders. For each participant, 3 sets of 10 words with specific blends in the initial position were targeted for training. Vocal imitation training with within-stimulus prompts was used for both participants. For KS, lip-tongue-teeth position prompts and chaining were added during the training of certain words. A multiple-baseline across-behaviors (word sets with target blends) design demonstrated improvement in the articulation of trained words and generalization of correct articulation to untrained words with both participants. The findings suggest that speech sound disorders in children with autism can be addressed with behavioral interventions.