piperidines and Alopecia

Topics: Alopecia; Alopecia Areata; Humans; Piperidines

Alopecia Areata is a nonscarring hair loss disorder and is the most common hair loss cause in children. It is a chronic autoimmune disorder with a severe psychological impact in patients' lives. JAK inhibitors, in particular Tofacitinib, have been having promising results on Alopecia Areata Treatment. In this study we aimed to do a Systematic Review on the role of Tofacitinib (either orally or topically), considering efficacy and safety, in treating children with Alopecia Areata.. PubMed, Cochrane and Web of Science databases were searched (up to 1st of September of 2021) looking for Tofacitinib (all text/all fields) and MeSH/Keyword term Alopecia Areata.. We included 14 studies and 64 cases in the Systematic Review. From these, 12 were considering systemic administration (47 patients) and two were considering topical administration (17 patients). Responsiveness was as high as 81.3%. The responsiveness was similar among different genders (78.6% in males and 80.0% in females) and either whether administration was topic (70.6% responsiveness) or systemic (85.1% responsiveness). Adverse effects were rare and, when present, were mild. Studies shows promising results in what considers the efficacy and safety of Tofacitinib in the treatment of Alopecia Areata. As the available evidence to date is of low quality, further randomised studies are required to confirm these findings.

Topics: Alopecia; Alopecia Areata; Child; Female; Humans; Male; Piperidines; Pyrimidines

The treatment of hair loss is a challenge for all dermatologists. New medications are needed due to lack of efficacy of many treatments or their side-effect profile. This article discusses the most recent literature updates on the use of retinoids in frontal fibrosing alopecia, platelet-rich plasma in androgenetic alopecia, and JAK inhibitors in alopecia areata.

Topics: 5-alpha Reductase Inhibitors; Alopecia; Alopecia Areata; Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Platelet-Rich Plasma; Purines; Pyrazoles; Pyrimidines; Pyrroles; Retinoids; Sulfonamides

Alopecia areata (AA) is a common autoimmune disorder characterized by patchy hair loss. There are many treatments available for AA. However, treatments of severe forms of AA are not satisfactory. Recently, oral Janus kinase (JAK) inhibitors were found to be effective for the treatment of severe AA variants.. The aim of this work was to evaluate and compare the efficacy, side effects, and durability of two oral JAK inhibitor medications (ruxolitinib and tofacitinib) in the treatment of severe AA.. This study included 75 patients with AA with more than 30% scalp hair loss, alopecia totalis, and alopecia universalis randomized into 2 groups. The first group (n = 38) received ruxolitinib 20 mg twice daily, and the second group (n = 37) received oral tofacitinib 5 mg twice daily. The treatment continued for 6 months followed by 3 months of follow-up off therapy. Efficacy of treatment was assessed by monitoring the change in the Severity of Alopecia Tool (SALT) score.. Both tofacitinib and ruxolitinib induced remarkable hair regrowth, with a mean change in SALT score of 93.8 ± 3.25 in the ruxolitinib group and 95.2 ± 2.69 in the tofacitinib group. However, the ruxolitinib group showed a shorter duration for initial hair regrowth. There was no statistically significant difference between the groups regarding hair regrowth at the end of the 6-month treatment and relapse rate at the end of the 3-month follow-up. Around two thirds of cases experienced relapse. Both drugs were well tolerated, with no reported serious adverse effects.. Both ruxolitinib and tofacitinib could be considered effective and well-tolerated treatments for extensive AA.

Topics: Administration, Oral; Adolescent; Adult; Alopecia; Alopecia Areata; Female; Hair; Humans; Janus Kinase Inhibitors; Male; Middle Aged; Nitriles; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Recurrence; Severity of Illness Index; Time Factors; Young Adult

Oral Janus kinase (JAK) inhibitors are currently being investigated in phase II and phase III clinical trials for several inflammatory skin diseases including alopecia areata (AA). Topical JAK inhibitors have been investigated in atopic dermatitis, psoriasis, and AA. While a number of case series using topical JAK inhibitors in AA have been published, to date there have been no randomized controlled clinical trials.. We conducted a phase I, 28 week prospective, placebo-controlled, double-blind study in patients with alopecia universalis investigating hair regrowth with two topical JAK inhibitors, 2% tofacitinib and 1% ruxolitinib. Topical clobetasol dipropionate 0.005% was the active comparator while vehicle was used as the placebo control. Sixteen patients were recruited for the study.. Six patients demonstrated partial hair regrowth in areas treated with 2% tofacitinib ointment applied twice daily. Five patients demonstrated partial hair regrowth in the areas treated with 1% ruxolitinib ointment. Ten patients demonstrated partial hair regrowth in the areas treated with clobetasol dipropionate 0.05% ointment. No regrowth was observed in the placebo treated area. Interestingly, generalized hair regrowth was observed in two patients. One patient had 100% regrowth over his entire scalp and eyebrows by week 24 but relapsed after 12 weeks. A second patient also experienced generalized scalp regrowth and significant eyebrow growth and continued to maintain growth 14 weeks later.. Our findings suggest that topical JAK inhibitors could be developed as a potential new treatment for AA and alternative to clobetasol dipropionate 0.05% ointment.

Topics: Administration, Cutaneous; Alopecia; Clobetasol; Double-Blind Method; Glucocorticoids; Hair; Humans; Janus Kinase Inhibitors; Nitriles; Ointments; Pilot Projects; Piperidines; Prospective Studies; Pyrazoles; Pyrimidines; Pyrroles

The purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic chemotherapy (MEC).. Predominantly female patients (98%) diagnosed with breast cancer (96%) who were chemotherapy-naïve and scheduled to receive an anthracycline and cyclophosphamide (AC) -based regimen were enrolled onto this multinational, randomized, double-blind, parallel-group, placebo-controlled clinical trial. All patients received dexamethasone 8 mg intravenously (IV) on day 1 and oral ondansetron 8 mg twice daily on days 1 to 3. Patients were randomly assigned to a control arm (placebo), a single oral dose casopitant arm (150 mg orally [PO] on day 1), a 3-day oral casopitant arm (150 mg PO on day 1 plus 50 mg PO on days 2 to 3), or a 3-day IV/oral casopitant arm (90 mg IV on day 1 plus 50 mg PO on days 2 to 3). The primary end point was the proportion of patients achieving complete response (no vomiting/retching or rescue medications) in the first 120 hours after the initiation of MEC.. A significantly greater proportion of patients in the single-dose oral casopitant arm, 3-day oral casopitant arm, and 3-day IV/oral casopitant arm achieved complete response (73%, 73%, and 74%, respectively) versus control (59%; P < .0001). The study did not demonstrate a reduced proportion of patients with nausea or significant nausea in those receiving casopitant. Adverse events were balanced among study arms.. All casopitant regimens studied were more effective than the control regimen. Casopitant was generally well tolerated.

Topics: Administration, Oral; Alopecia; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Constipation; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Headache; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Neutropenia; Ondansetron; Piperazines; Piperidines; Treatment Outcome; Vomiting

Topics: Alopecia; Alopecia Areata; COVID-19; Humans; Piperidines; Pyrroles

Alopecia areata (AA) is an autoimmune disorder characterized by nonscarring hair loss that can involve the scalp, face, and body. Severe AA subtypes have a poorer prognosis and can be challenging to treat. Tofacitinib, a recently introduced Janus kinase inhibitor, has shown positive results in treating AA. This multicenter study demonstrates the efficacy of tofacitinib and the patient response rate in a Saudi population. It also highlights patient characteristics that may serve as predictors of the therapeutic response to tofacitinib.. A prospective cohort study design was utilized. Study participants were included from three medical centers in Riyadh, Saudi Arabia. The Severity of Alopecia Tool (SALT) score was used to assess the percentage of hair loss at baseline and the percentage of hair regrowth at 3 and 6 months.. The sample size was 68 with an average baseline SALT score of 76.8 ± 27.6%. Data at 6 months were available for 45 patients. Of these, 62.2% achieved a SALT score of >50%. Patients with a score of <50% had a significantly higher baseline SALT score compared to patients with >50% score. The past use of systemic steroids was associated with a diminished response to therapy (P = 0.015). The response to therapy was significantly higher in patients with AA compared to alopecia totalis and alopecia universalis.. Tofacitinib is an effective and well-tolerated treatment for severe AA and exhibits a good safety profile.

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Prospective Studies; Pyrimidines; Pyrroles; Saudi Arabia; Treatment Outcome

Alopecia areata (AA) is characterized by the loss of hair, often in well-demarcated areas. While the pathogenesis of AA is not entirely understood, it is known that CD8 T cell-mediated destruction of the hair follicle occurs. There are no curative therapies for AA, although several therapies have been utilized with variable results. Oral tofacitinib, a JAK inhibitor, has been demonstrated to be efficacious and well tolerated in the treatment of adult AA. However, few studies have examined the clinical efficacy and tolerability of oral tofacitinib in the treatment of pediatric AA.. To summarize the clinical outcomes of pediatric patients with AA treated with oral tofacitinib at the University of Colorado Hospital Dermatology Clinic.. This is a retrospective case series conducted at the University of Colorado Hospital Dermatology Clinic. We included patients with a diagnosis of AA who were 18 years old or younger at the initiation of tofacitinib therapy. Demographics, treatment response, and adverse events were collected from electronic medical records.. Eleven patients (seven females, four males) with AA presented to the University of Colorado Hospital Dermatology Clinic who were between the ages of 8 and 18 years. Eight patients (72.7%) experienced hair regrowth with oral tofacitinib, while three patients (27.3%) experienced minimal to no hair regrowth. There were no serious adverse events recorded in the study population during the observed treatment period.. Oral tofacitinib was clinically effective in the majority our of patients and well tolerated.

Topics: Adolescent; Alopecia; Alopecia Areata; Child; Female; Humans; Male; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies; Treatment Outcome

Alopecia areata (AA) is an immune-mediated hair loss disease for which targeted immune treatments including Janus kinase (JAK) inhibitors, for example, tofacitinib, are emerging. More literature is needed on the safety and efficacy of JAK inhibitors, and treatment has the potential to be cost prohibitive. This study was conducted to measure safety and efficacy outcomes of off-label use of tofacitinib in AA. A secondary outcome was analysis of payment methods. We reviewed 35 AA patients treated with tofacitinib in a specialty hair disease clinic between January 2013 and July 2019 for outcomes, adverse events, and feasibility of treatment. No serious adverse events were experienced. 83.9% of patients experienced clinically significant scalp regrowth, and 32.3% experienced near total/total regrowth. Though this study was confined to retrospective analysis, the results showed that tofacitinib was safe, effective, and practical for this cohort of 35 AA patients.

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies

Dermatomyositis (DM) and alopecia areata are two diseases characterised by aberrant interferon signalling. While patchy alopecia of the scalp is a known feature of DM, alopecia universalis, which involves hair loss over the entire body, has rarely been reported in conjunction with DM. Herein, we report the case of a 30-year-old female with DM who developed refractory cutaneous disease and alopecia universalis that were successfully treated with tofacitinib. This could suggest that concomitant severe alopecia and refractory cutaneous DM may reflect a strong baseline interferon gene signature that may predict responsiveness to janus kinase inhibitors.

Topics: Adult; Alopecia; Alopecia Areata; Dermatomyositis; Female; Humans; Interferons; Piperidines; Pyrimidines; Pyrroles

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

Alopecia universalis (AU) is an autoimmune disorder characterized by non-scarring hair loss in the scalp, eyebrows, beard, and nearly the entire body, negatively affecting patient prognosis. Available treatments are usually unsatisfactory. The autoimmune attacks of hair follicles induced by CD8+ T cells and the collapse of hair follicle immune privilege are believed to be the leading causes of AU. Additionally, interferon (IFN)-γ plays an important role in triggering the collapse of hair follicle immune privilege and impairing hair follicle stem cells. Furthermore, the upregulation of Janus kinase (JAK)3 and phospho-signal transducer and activator of transcription (pSTAT)3/STAT1 in alopecia areata patients suggest that JAK inhibitors can be a potentially promising choice for AU patients for the reason that JAK inhibitors can interfere with JAK-STAT signaling pathways and inhibit IFN-γ. Herein, we report a case of AU successfully treated with tofacitinib. However, this beneficial response in the patient was accompanied by a remarkable increase in peripheral blood cytokine levels during tofacitinib treatment.

Topics: Alopecia; Alopecia Areata; Cytokines; Humans; Janus Kinase Inhibitors; Piperidines; Pyrimidines

Topics: Alopecia; Alopecia Areata; Child, Preschool; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Alopecia; Alopecia Areata; Child; Humans; Piperidines; Pyrimidines; Pyrroles; Young Adult

Topics: Administration, Topical; Alopecia; Alopecia Areata; Humans; Minoxidil; Piperidines; Pyrimidines

Topics: Alopecia; Colitis, Ulcerative; Dermatitis, Atopic; Humans; Piperidines; Pyrimidines

We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2 × 5 mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.. Wir präsentieren den Fall einer 46-jährigen Patientin, die an einer entzündlich aktiven Alopecia areata universalis leidet. Nach frustranem Einsatz von topischen und systemischen Glukokortikoiden, einer Creme-PUVA-Therapie und Dithranol in aufsteigender Dosierung wurde die Patientin mit 2‑mal 5 mg pro Tag Tofacitinib per os behandelt. Nach ca. 4 bis 6 Monaten zeigte die Patientin ein Haarwachstum, das bei guter Verträglichkeit bis zum 18. Therapiemonat zur vollständigen Wiederbehaarung geführt hat. Der Fall zeigt eindrucksvoll, dass die Off-label-Anwendung von Tofacitinib eine potenzielle therapeutische Option in der Indikation Alopecia areata darstellen kann.

Topics: Alopecia; Alopecia Areata; Female; Humans; Middle Aged; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is an autoimmune nonscarring alopecic disorder, which presents with varying amounts of hair loss, ranging from focal patchy loss to entire scalp and body hair loss. Treatment of AA is a challenging issue within dermatology practice. Although many treatment options are present, response to medications remains unsatisfactory, especially in severe and recalcitrant cases. In this study, we present a case of treatment-resistant AU, which was successfully treated by the combination of tofacitinib and oral minoxidil.

Topics: Alopecia; Alopecia Areata; Humans; Minoxidil; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is an autoimmune hair loss condition that affects people of all ages. Early age of onset and prolonged disease duration indicate poor prognosis. Janus kinase inhibitors are being investigated in phase 3 clinical trials in adolescents and adults with AA OBJECTIVE: To evaluate the use of oral tofacitinib in pre-adolescent patients with AA.. A retrospective review of case records of all pre-adolescent patients with AA treated with oral tofacitinib in a single center between 2018 and 2019.. Fourteen patients were identified, aged 7 to 11 years. Nine patients experienced clinically significant improvement in their SALT (Severity of Alopecia Tool) score. Three patients achieved complete remission (SALT score of 0), seven (63.6%) achieved over 50% improvement in SALT score from baseline. One patient had no change from baseline, another experienced additional hair loss. After an average of 9 months of treatment, the median SALT score improvement was 67.7%. The improvement was similar in patients with baseline SALT scores greater than 50 and those with baseline SALT scores below 10. Adverse events were mild.. The retrospective nature of the data, small sample size, lack of a control group, referral bias to a specialist hair center, and concomitant use of other medications including oral minoxidil in all patients.. There is a role for tofacitinib as a systemic therapy in AA and this should be further evaluated in prospective clinical trials in pre-adolescents.

Topics: Adolescent; Adult; Alopecia; Alopecia Areata; Child; Humans; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies

Topics: Alopecia; Female; Humans; Janus Kinase Inhibitors; Lichen Planus; Middle Aged; Nail Diseases; Piperidines; Pyrimidines; Treatment Outcome

Topics: Alopecia; Alopecia Areata; Child; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Adult; Alopecia; Female; Humans; Janus Kinase Inhibitors; Life Change Events; Piperidines; Pyrimidines

Topics: Administration, Topical; Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Alopecia; Folliculitis; Humans; Piperidines; Pyrimidines; Pyrroles

Alopecia totalis (AT) is characterised by extensive hair loss on the scalp, and common treatments are rarely effective. Janus kinase inhibitors represent a potentially new treatment modality in AT. In this case report, AT was successfully treated with tofacitinib in a 43-year-old male patient. After six months of treatment, the patient regained all his hair, and no relapse was seen after one year of treatment.

Topics: Adult; Alopecia; Denmark; Humans; Male; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is a common disease that results in nonscarring hair loss. Recently, tofacitinib (TOFA) has been a novel promising therapy for AA. The aim of this study is to determine the efficacy of oral TOFA treatment for alopecia areata (AA), and alopecia universalis (AU). Data of nine patients treated with oral TOFA with either AA or AU were retrospectively evaluated. Treatment outcome, disease severity, and therapeutic response were evaluated by Severity of Alopecia Tool (SALT) scores along with regular photographic surveillance done at third and sixth months. Treatment response was established on four categories: complete response (90% change in latest SALT score), intermediate response (51-90% change), moderate response (6-50% change), and nonresponse (<5% change). Nine patients aged 13-33 years were reviewed. Four patients (44.4%) did not respond to oral TOFA therapy, three patients (33.3%) were moderate responders, 1 (11.1%) was intermediate responder, and 1 (11.1%) was complete responder at the end of 6 months. The clinical response rate (those who achieved ≥5-100% change in SALT score) was 41.4% for all patients. Most of the patients who responded to TOFA had AA instead of AU. Adverse effects were mild. The clinical response rate of TOFA seems reasonable and TOFA was well-tolerated in this cohort. However, to truly evaluate efficacy, future studies are needed to assess the efficacy, adverse effects, and durability of treatment with TOFA in randomized controlled trials.

Topics: Administration, Oral; Adolescent; Adult; Alopecia; Alopecia Areata; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Treatment Outcome; Young Adult

Treatment of alopecia totalis and alopecia universalis is often challenging and unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The aim of this study is to compare the efficacy and tolerability of oral tofacitinib and conventional modalities for treating refractory alopecia totalis/universalis. A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional oral treatment (steroid ± cyclosporine), and 30 treated with diphenylcyclopropenone) were included in the study. The patients' medical records were reviewed retrospectively. After 6 months, 44.4% of patients in the tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in the diphenylcyclopropenone group achieved 50% improvements in the Severity of Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group, 73.1% in the conventional oral treatment group, and 10% in the diphenylcyclopropenone group experienced adverse drug reactions. In conclusion, oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and more tolerable than conventional oral treatment after 6 months of treatment.

Topics: Administration, Oral; Adolescent; Adult; Alopecia; Cyclopropanes; Cyclosporine; Female; Humans; Immunosuppressive Agents; Janus Kinase Inhibitors; Male; Middle Aged; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies; Steroids; Time Factors; Treatment Outcome; Young Adult

Topics: Alopecia; Alopecia Areata; Child, Preschool; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Severity of Illness Index

Topics: Adult; Alopecia; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles

Ebastine is a second-generation histamine H1 receptor antagonist that is used to attenuate allergic inflammation. Ebastine has also shown to affect hair loss; however, the immunoregulatory effect of ebastine cannot completely exclude the possibility of spontaneous hair regrowth in ebastine-treated mice. In this study, we examined the effects of ebastine on the growth of human follicle dermal papilla cells (HFDPC) using a WST-1 cell proliferation assay and a bromodeoxyuridine incorporation assay. Ebastine was shown to significantly increase the proliferation of HFDPC. The expression levels of cell-cycle regulatory proteins and an antiapoptotic protein were increased in ebastine-treated HFDPC. Furthermore, elevated expression levels of phospho-AKT and phospho-p44/42 extracellular signal-regulated kinase (ERK) were observed in ebastine-treated HFDPC. Ebastine-mediated HFDPC growth was completely reversed by blocking ERK kinase. The results from our present study suggest that the regulation of HFDPC proliferation by ebastine might be directly involved in hair regrowth through the ERK signaling pathway.

Topics: Alopecia; Apoptosis; Butyrophenones; Cell Line; Cell Proliferation; Dermis; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Hair; Hair Follicle; Humans; Mitogen-Activated Protein Kinase 3; Piperidines; Proto-Oncogene Proteins c-akt

Topics: Alopecia; Drug Eruptions; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Urticaria; Young Adult

Topics: Administration, Topical; Adolescent; Alopecia; Alopecia Areata; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hair; Humans; Male; Pediatrics; Piperidines; Pyrimidines; Pyrroles; Sampling Studies; Treatment Outcome

Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia for which many different therapies are attempted with varying success. The Janus kinase (JAK) inhibitor, tofacitinib, has been shown to be effective in treating the noncicatricial alopecia, alopecia areata. As in alopecia areata, upregulation of interferon and JAK signaling may play a role in LPP. We retrospectively reviewed the cases of 10 patients with recalcitrant LPP who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg twice or three times daily for 2-19 months as either monotherapy or adjunctive therapy to other ongoing treatments including intralesional triamcinolone, hydroxychloroquine, and tacrolimus ointment. Eight patients had clinical improvement in LPP with tofacitinib as either monotherapy (4/10) or adjunctive therapy (4/10). LPP Activity Index (LPPAI) before and after treatment was measured in seven patients and was significantly different (6.22 before treatment, 3.08 after treatment; p value = .0014). Reduction in LPPAI ranged from 30 to 94%. One patient complained of 10 pound (4.5 kg) weight gain after 12 months on tofacitinib. No other adverse effects were reported. Treatment with oral tofacitinib either as monotherapy or adjunctive therapy can lead to measurable improvement in recalcitrant LPP.

Topics: Administration, Oral; Adult; Aged; Alopecia; Dermatologic Agents; Drug Administration Schedule; Female; Humans; Janus Kinase Inhibitors; Lichen Planus; Male; Middle Aged; Piperidines; Pyrimidines; Pyrroles; Remission Induction; Retrospective Studies; Scalp; Scalp Dermatoses; Skin; Time Factors; Treatment Outcome

Topics: Administration, Oral; Adolescent; Alopecia; Child; Dermatologic Agents; Humans; Janus Kinase 1; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome; Young Adult

Topics: Adult; Alopecia; Female; Humans; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome

Topics: Administration, Oral; Alopecia; Drug Therapy, Combination; Glucocorticoids; Humans; Injections, Intralesional; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Triamcinolone; Young Adult

Alopecia universalis (AU) is generally considered a variant of alopecia areata (AA), in which the treatment options seldom provide satisfactory results. However, successful treatment of several cases of AA and its variants with oral Janus kinase (JAK) inhibitors have been reported recently. Here we report a 23-year-old female patient with AU successfully treated with tofacitinib, a selective JAK-3 inhibitor. The initial tofacitinib dose was 5 mg twice daily. After 2 months of treatment, partial hair regrowth was seen on the scalp and eyebrows. Thereafter, the dose was increased to 10 mg in the morning and 5 mg at night. By 6 months of the treatment, there was complete hair regrowth throughout the entire body. Our patient tolerated tofacitinib well, without any significant side effects. Tofacitinib emerges as a promising novel therapy in alopecia universalis. We believe further study is required to establish the safety and confirm the efficacy of tofacitinib treatment for alopecia universalis.

Topics: Alopecia; Female; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Young Adult

Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P < 0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P < 0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P < 0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.

Topics: Administration, Topical; Alopecia; Animals; Hair; Janus Kinase 3; Male; Mice; Mice, Inbred C57BL; Minoxidil; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Vascular Endothelial Growth Factor A

Topics: Adolescent; Alopecia; Alopecia Areata; Arthritis, Psoriatic; Female; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retreatment

There are no reliably effective therapies for alopecia areata (AA).. 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.. 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.. 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 include the retrospective nature of the data, small sample size, and lack of a control group.. 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.

Topics: Adolescent; Alopecia; Alopecia Areata; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA.. 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.. 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.. 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.. The retrospective nature of the data, the relatively small number of patients, and lack of a control group are limitations.. 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.

Topics: Adolescent; Adult; Aged; Alopecia; Alopecia Areata; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

Nail dystrophy is a heterogeneous skin condition and in some subtypes, is associated with autoimmune diseases in particular psoriasis and psoriatic arthritis. In this report, we show that tofacitinib, a novel therapy for rheumatoid arthritis, appears to be beneficial in patients with nail disease refractory to other conventional modes of therapy.

Topics: Adult; Alopecia; Female; Humans; Male; Nail Diseases; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome

Topics: Adult; Alopecia; Female; Humans; Janus Kinases; Male; Nail Diseases; Nails; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles

Autoimmune-triggered non-scarring hair loss is a feature of alopecia areata (AA). Initially patchy and often self-limited, severe hair loss forms include the complete loss of scalp hair or alopecia totalis (AT) and complete loss of all hair or alopecia universalis (AU). For AT and AU a reliable treatment has remained elusive. The targeted kinase inhibitor tofacitinib, in current use for treatment of other immune diseases, has been hypothesized as a viable option for AA, AT and AU therapy and a few case reports support this.. Our study aims to provide evidence for the effectiveness of tofacitinib in the treatment of AU.. Two patients diagnosed with long-term AU were prescribed tofacitinib citrate at a dosage of 5 mg twice daily and observed for eight months.. In the first patient, beard growth was significant by 3 months of treatment. By 6 months of treatment, hair growth was apparent throughout the entire body. By 8 months of treatment, scalp hair continued to grow longer and thicker. In addition, eyelashes and eyebrows were established. In the second patient, a noticeable increase in scalp hair was present just 1 month into treatment. By 4 months into treatment, significant scalp regrowth was observed as well as eyelash, eyebrow and beard regrowth. Axillary hair regrowth and isolated leg hair was noted by 8 months.. In our patients, tofacitinib successfully alleviated AU in the absence of significant adverse side-effects. We recommend that further study be required to establish safety and confirm efficacy.

Topics: Adult; Alopecia; Humans; Male; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome

Topics: Adult; Alopecia; Female; Humans; Janus Kinase 1; Janus Kinase 3; Janus Kinase Inhibitors; Male; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome; Young Adult

Topics: Alopecia; Humans; Male; Piperidines; Psoriasis; Pyrimidines; Pyrroles

Topics: Adult; Alopecia; Dose-Response Relationship, Drug; Humans; Male; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Treatment Outcome

We investigated the involvement of substance P (SP) and the neurokinin-1 receptor (NK(1)R) in the development of radiation-induced hair loss in mice. A dose of 40 Gy of gamma irradiation induced hair loss from the 10th to at least the 60th day after irradiation. A specific NK(1)R antagonist, CP-99,994, significantly delayed radiation-induced hair loss and reduced its severity. Furthermore, gamma irradiation induced the expression of preprotachykinin-A, a precursor protein of SP, mRNA in irradiated murine skin on the 10th and 30th days after irradiation. These results indicated that gamma irradiation-induced hair loss was mediated by SP via NK(1)R.

Topics: Alopecia; Animals; Male; Mice; Mice, Inbred C57BL; Neurokinin-1 Receptor Antagonists; Piperidines; Protein Precursors; Radiation Injuries, Experimental; Receptors, Neurokinin-1; Substance P; Tachykinins