Lucy Y. Liu

Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients.

Background: Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA. Objective: We sought to evaluate the safety and efficacy of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of patients over an extended period of time. Methods: This is a retrospective study of patients age 18 years or older with AA with at least 40% scalp hair loss treated with tofacitinib. The primary end point was the percent change in Severity of Alopecia Tool (SALT) score during treatment. Results: Ninety patients met inclusion criteria. Of 65 potential responders to therapy, defined as those with alopecia totalis or alopecia universalis with duration of current episode of disease of 10 years or less or alopecia areata, 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in SALT score over 4 to 18 months of treatment. Patients with AA experienced a higher percent change in SALT score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events. Limitations: The retrospective nature of the data, the relatively small number of patients, and lack of a control group are limitations. Conclusion: Tofacitinib should be considered for the treatment of severe AA, alopecia totalis, and alopecia universalis; tofacitinib dose response will be better defined by randomized controlled trials.

Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting

BACKGROUND Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES). Here we present our initial results. METHODS The WES was performed in 102 patients (mean age 56.8 years; range 13 to 83; 70 males [68.6%]) with TAAD. The following 21-gene panel was tested by WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2. RESULTS Seventy-four patients (72.5%) had no medically important genetic alterations. Four patients (3.9%) had a deleterious mutation identified in the FBN1, COL5A1, MYLK, and FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants of unknown significance were identified in 1 or more of the following genes: FBN1 (n = 5); MYH11 (n = 4); ACTA2 (n = 2); COL1A1 (n = 2); TGFBR1 (n = 2); COL3A1 (n = 1); COL5A1 (n = 1); COL5A2 (n = 1); FLNA (n = 1); NOTCH1 (n = 1); PRKG1 (n = 1); and TGFBR3 (n = 1). Identified mutations had implications for clinical management. CONCLUSIONS Routine genetic screening of patients with TAAD provides information that enables genetically personalized care and permits identification of novel mutations responsible for aortic pathology. Analysis of large data sets of variants of unknown significance that include associated clinical features will help define the mutational spectrum of known genes underlying this phenotype and potential identify new candidate loci.

Tofacitinib for the treatment of alopecia areata and variants in adolescents

Background: There are no reliably effective therapies for alopecia areata (AA). Objective: We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA. Methods: We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems. Results: Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%‐100%) at an average of 6.5 months of treatment. Adverse events were mild. Limitations: Limitations include the retrospective nature of the data, small sample size, and lack of a control group. Conclusion: Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials.

Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure

Background: Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. Objective: To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo. Method: This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. Results: Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low‐dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration. Limitations: Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group. Conclusion: Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low‐level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.

Pathologic leadpoint is uncommon in ileo-colic intussusception regardless of age

PURPOSE Historically, the rate of pathologic leadpoints in older children with intussusception is quoted as 20%-25%. Our anecdotal experience suggested a lower rate. We therefore compiled a case series to examine the actual incidence of pathologic leadpoint, and treatment success, by age. METHODS A retrospective review was performed of all patients admitted with intussusception between 1998 and 2012 and tested for differences in anatomic location, presence of pathologic leadpoint, and need for operative intervention, on the basis of age. RESULTS In total, 154 cases of intussusception were diagnosed in 141 patients (136 ileo-colic), 38 of which were in children older than 3 (29 ileo-colic). Considering all anatomic locations, older children were more likely to have a pathologic leadpoint (p-value 0.01); however subgroup analysis of ileo-colic intussusception demonstrated no difference (p-value 0.38). Additionally, there was no difference in the success of pneumatic or barium enema reduction on the basis of age (p-value 0.56). CONCLUSION Despite historical reports of increased pathologic leadpoints in ileo-colic intussusception in older children, in this series the majority were idiopathic. Non-operative management was successful approximately 75% of the time, irrespective of age. In older age groups, there was an increased frequency of pathologic leadpoints in small bowel-small bowel intussusception.

Neuromonitoring Using Motor and Somatosensory Evoked Potentials in Aortic Surgery

Motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) are established methods of neuromonitoring aimed at preventing paraplegia after descending or thoracoabdominal aortic repair. However, their predictive impact remains controversial. The aim of this study was to evaluate our single‐center experience using this monitoring technique.

Tofacitinib 2% ointment, a topical Janus kinase inhibitor, for the treatment of alopecia areata: A pilot study of 10 patients

To the Editor: Alopecia areata (AA) is a common autoimmune disease. Although oral Janus kinase (JAK) inhibitors have emerged as promising targeted treatment for AA, data regarding topical JAK inhibitors are lacking. Here, we describe the results of a 24-week, openlabel, single-center pilot study of 10 patients with AA treated with tofacitinib 2% ointment applied twice daily. Inclusion criteria included

Lack of efficacy of apremilast in 9 patients with severe alopecia areata

18 years of age, AA with

Alopecia areata is associated with impaired health-related quality of life: A survey of affected adults and children and their families

2 patches of scalp hair loss or complete scalp hair loss, stable or worsening disease for

Tofacitinib for the Treatment of Severe Alopecia Areata in Adults and Adolescents

6 months, and no treatment of AA for