Hemihyperplasia-multiple lipomatosis syndrome (HHML) is a condition characterized by asymmetric nonprogressive overgrowth, multiple lipomas, and superficial vascular malformations. We present two cases of HHML to enhance the diagnostic acumen of dermatologists and avoid potential misdiagnosis of this rare but probably underrecognized entity. We also provide a brief review of asymmetric overgrowth syndromes, which have overlapping yet distinct clinical manifestations.
Abstract Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long‐term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.
Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score <2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age. Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (<12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS <2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS <2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P<0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (<12 years; both P<0.0001). Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.
Importance: Ectropion is a complication of certain subtypes of ichthyosis and is often associated with substantial medical and cosmetic consequences.At present there is no standard of care for the treatment of ectropion in this population.Retinoids cause dyshesion and thinning of stratum corneum, thereby reducing hyperkeratosis that likely underlies ectropion in patients with ichthyosis.As such, retinoids provide a potential effective treatment for ectropion in this group of patients.Observation: We describe a patient with recessive ichthyosis for whom daily application of topical tazarotene produced rapid and persistent improvement of bilateral lower eyelid ectropion without adverse effects.
Harlequin ichthyosis (HI) is the most severe phenotype of the autosomal recessive congenital ichthyoses. HI is caused by mutations in the lipid transporter adenosine triphosphate binding cassette A 12 (ABCA12). Neonates are born with a distinct clinical appearance, encased in a dense, platelike keratotic scale separated by deep erythematous fissures. Facial features are distorted by severe ectropion, eclabium, flattened nose, and rudimentary ears. Skin barrier function is markedly impaired, which can lead to hypernatremic dehydration, impaired thermoregulation, increased metabolic demands, and increased risk of respiratory dysfunction and infection. Historically, infants with HI did not survive beyond the neonatal period; however, recent advances in neonatal intensive care and coordinated multidisciplinary management have greatly improved survival. In this review, the authors combine the growing HI literature with their collective experiences to provide a comprehensive review of the management of neonates with HI.
Abstract Alopecia areata (AA) is a common, immune-mediated, nonscarring alopecia associated with increased risk of other autoimmune conditions such as thyroid disease. Risk of cardiovascular disease in AA is contentious, but is relevant in the era of Janus kinase (JAK) inhibitor therapy. Rarely, nutritional deficiency and infective disorders, such as syphilis, can mimic AA. International guidelines, including those issued by the British Association of Dermatologists, recommend that investigations are unnecessary when patients are asymptomatic for other conditions. Despite guidelines, there is diversity among experts in AA with respect to laboratory investigation, which this study aimed to describe. Thirty dermatologists specializing in hair disorders from 14 countries and six continents contributed to development of a survey to investigate variation in expert practice regarding laboratory testing in AA. The survey was distributed via Google Forms among expert hair networks globally. Of 130 dermatologists, 73.1% (n = 95) had a subspecialty interest in hair disorders. Almost all (87.7%, n = 114) saw both children and adults with AA. There was a global spread, with 41.5% (n = 54) from Europe, 23.1% (n = 30) from Asia and 13.8% (n = 18) from Africa. For one-quarter (26.4%) of respondents, hair loss disorders represented > 50% of their patients. Almost two-thirds (63.8%) did not perform anthropometry, while 66.2% used the Severity of Alopecia Tool and 39.2% used the Dermatology Life Quality Index. Over half (51.5%) routinely or always performed screening bloods for coexisting autoimmune illness (e.g. thyroid disease or coeliac disease), 39.2% routinely performed screening bloods for contributory conditions (e.g. nutritional deficiencies or endocrine disease), and 18.6% routinely screen for alternative diagnoses (e.g. syphilis) in all patients with AA. Regarding the identification of comorbidities, 70.8% routinely ordered thyroid testing, 65.4% ordered full blood counts, and 46.9% requested liver function testing. Before starting conventional systemic therapy (e.g. ciclosporin or methotrexate), 80.8% ordered full blood counts, 79.2% liver function, 73.8% renal function, 66.7% hepatitis B and C serology, 57.7% HIV testing, and 53.1% lipid testing. Before starting JAK inhibitors, 89.8% ordered full blood counts, 88% liver function tests, 73.8% renal function tests, 67.7% hepatitis B and C serology, 65.4% tuberculosis testing, 62.3% lipid testing, and 56.2% HIV testing. Three-monthly monitoring was conducted by 59.4%. This study identifies that real-world practice among AA experts (who may see more severe or complex AA) is variable with respect to laboratory testing, and that a renewed discussion is warranted in this regard.
Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available.
Observations
Recent advances in the understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation.
Conclusions and Relevance
The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.
