Efficacy and safety of tofacitinib for treatment of alopecia areata in children: A systematic review and meta-analysis.

BACKGROUND: Tofacitinib, a potent JAK inhibitor, has gained increasing interest, in recent years, among dermatologists for the management of refractory alopecia areata. Despite a growing number of studies on its safety and efficacy, there is still a lack of clarity, especially in the pediatric population, in treatment considerations such as proper dosage, treatment duration, side-effect profile, and therapeutic strategies to guide clinicians. METHODS: Multiple databases were systematically searched. Following the PRISMA diagram, of a pool of 601 papers, seven met a checklist of inclusion criteria. These were observational studies including a total of 59 patients from four to 19 years of age. RESULTS: In the evaluated studies, tofacitinib was administered either orally at a 2.5 to 15 mg daily (mostly 5 mg twice a day) dosage for 2 to 38 months or in the form of a 2% topical solution for 3-17 months. Metanalysis showed that 49% (95% CI: 29%-69%, I2  = 59.94%) of patients experienced a reversal of alopecia after a minimum of 3 to 9 months of therapy. Fifty-five percent (95% CI: 23%-86%, I2  = 75.07%) and 41% (95% CI: 23%-59%, I2  = 0.00%) showed Good/complete and partial response rates, respectively. Oral administration was significantly more efficacious than topical application (73% vs 23%, p-Value = 0.04). Few side effects such as diarrhea and mild liver transaminases abnormalities were noted in several patients. CONCLUSION: Results of this review suggest that tofacitinib at 2.5-15 mg daily (especially 5 mg twice daily) oral formulation or 2% topical solution can be regarded as a viable alternative or adjunct to the conventional treatment options for moderate to severe forms of alopecia areata in children owing to its acceptable efficacy and side-effect profile. However, uncertainties continue to exist around treatment strategies including initial and maintenance dosages, route of administration, dose adjustments, the timing of tapering or discontinuation, and associated treatment modalities.

Platelet-rich plasma in the treatment of scars, to suggest or not to suggest? A systematic review and meta-analysis.

Despite the rising trend for applying platelet-rich plasma (PRP) in the management of various types of scars, there is no convincing evidence supporting its use. This motivated us to review the randomized clinical trials that examine the effectiveness and safety of PRP, alone or in combination with other methods, for the management of atrophic or hypertrophic/keloidal scars. The Web of Science, Scopus, Google Scholar, and Cochrane Library databases were systematically searched until September 1st , 2020. Thirteen clinical trials were enrolled in the meta-analysis, and 10 more were reviewed for their results. The random effect meta-analysis method was used to assess the effect size of each outcome for each treatment type, and I2 was used to calculate the statistical heterogeneity between the studies. Patients treated with PRP experienced an overall response rate of 23%, comparable to the results seen with laser or micro-needling (22% and 23%, respectively) When used alone, moderate improvement was the most frequently observed degree of response with PRP (36%) whereas, when added to laser or micro-needling, most patients experienced marked (33%, 43%, respectively) or excellent (32% and 23%, respectively) results. Concerning the hypertrophic/keloid scars, the only study meeting the required criteria reported a better improvement and fewer adverse effects when PRP was added to the intralesional corticosteroids. Platelet-rich plasma appears to be a safe and effective treatment for various types of atrophic scars. In addition, when added to ablative lasers or micro-needling, it seems to considerably add to the efficacy of treatment and reduce the side effects.

Efficacy, safety, tolerability, and satisfaction of N-acetylcysteine and pentoxifylline in lichen planopilaris patients under treatment with topical clobetasol: A triple arm blinded randomized controlled trial.

Lichen planoplaris (LPP) is one of the most common causes of inflammatory cicatricial alopecias. There is no definitive cure for the disease and most of the available therapeutic options can potentially lead to serious complications following their use for extended durations. In this study, we aimed to evaluate the efficacy, safety and tolerability of N-acetylcysteine (NAC) and pentoxyfillin (PTX), as adjunctive therapies, in the management of LPP. In a randomized, assessor- and analyst-blinded controlled trial, patients with proven LPP were randomly assigned to three groups of 10. Group I (the control group) received clobetasol 0.05%lotion; Group II, a combination of clobetasol 0.05% lotion and oral PTX; Group III, a combination of clobetasol lotion 0.05% and oral NAC. Lichen planopilaris activity index (LPPAI), the possible side effects, tolerability and patients satisfaction were assessed before and two and four months after the initiation of the treatments. Thirty patients, 96.7% women, with a mean age of 46.8 ± 13.3 years old, were included in the study. Four months into the treatments, the overall LPPAI and the severity and/or frequency of most of its determinants significantly decreased in all groups. In a comparison among the groups, patients who received either of the combination therapies showed more decline in their LPPAI than those receiving only clobetasol. The decline was more noticeable and statistically significant only in the NAC group. Three patients in the PTX group developed complications that were not statistically significant when compared with the other groups. There were no substantial differences in the tolerability of the treatments among the study arms. The use of oral NAC and PTX added to the therapeutic efficacy of topical clobetasol in the treatment of LPP, suggesting that they might be beneficial and safe adjuvant therapies and add to the efficacy of topical treatment without any noticeable impact on the adverse effects experienced by patients.

Temporal course of avascular femoral head necrosis in patients with pemphigus vulgaris.

BACKGROUND AND OBJECTIVES: Pemphigus vulgaris (PV) is typically treated with systemic corticosteroids and immunosuppressive agents. Avascular necrosis (AVN) of the femoral head is a well-recognized major complication of corticosteroid therapy. The characteristics of this serious complication in PV remain unknown. PATIENTS AND METHODS: Uncontrolled, retrospective study of all PV-related AVN cases diagnosed at an Iranian autoimmune bullous disease clinic between 1985 and 2013. RESULTS: Of the 2,321 medical records of PV patients reviewed, 45 (1.93 %) cases showed femoral AVN, with 30 (66.7 %) individuals being male. The mean age at diagnosis of AVN was 47.4 ± 14.2 years. The mean interval between the diagnosis of PV and the onset of AVN was 25.3 ± 18.3 months. With the exception of eight cases (17.8 %), the majority of patients developed AVN within three years after the diagnosis of PV. The mean cumulative dose of prednisolone in patients with AVN was 13,115.8 ± 7041.1 mg. There was a strong correlation between the total prednisolone dose and the time of onset of AVN (p = 0.001). In patients with a history of alendronate intake, that interval was significantly shorter (p = 0.01). CONCLUSIONS: Occurring in about 2 % of patients, AVN is a serious complication of corticosteroid treatment in patients with PV, predominantly in the first three years of treatment. In individuals receiving higher doses of prednisolone, AVN tends to occur earlier.

Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

HINTERGRUND UND ZIELE: Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. PATIENTEN UND METHODEN: Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. ERGEBNISSE: Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). SCHLUSSFOLGERUNGEN: Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein.

Nevus sebaceus: a clinicopathological study of 168 cases and review of the literature.

BACKGROUND: Nevus sebaceus is a hamartoma composed of abnormal epidermal and dermal components with clinical and histopathological features that change with aging. Prophylactic excision of the lesion was advised historically considering its potential for giving rise to malignant tumors. However, whether early prophylactic excision should be performed has been questioned recently as most of the tumors have been found to be benign in origin. METHODS: The histopathologic features of 168 patients with nevus sebaceus were reviewed to determine the frequency of different histologic features as well as associated neoplastic growths. RESULTS: Acanthosis, papillomatosis, and basal layer pigmentation were the most frequent findings. Hyperplastic changes of the sebaceous glands became obvious during the second decade and were present in 60% of the specimens from individuals older than 20. Inflammatory infiltrate was almost invariably present. Skin adnexal changes were frequently noted, including sebaceous gland hyperplasia (93.5%) and primitive hair follicles (76.8%). In 88.5% of scalp lesions, markedly decreased terminal hair was observed. Ectopic apocrine glands were present in 55.4% of specimens, while 24.4% showed anomalous ductal sweat gland structures resembling eccrine hyperplasia. Neoplastic changes were detected in nine cases, including four trichoblastomas, three tricholemmomas, and two syringocystadenoma papilliferums. CONCLUSION: Development of malignancies in sebaceus nevi is a rare phenomenon, and decision for excision of the lesion should be made after thorough evaluation of the pros and cons.

Frequency of seropositivity against infectious agents amongst pemphigus vulgaris patients: a case-control study on Strongyloides stercoralis, Helicobacter pylori, Toxoplasma gondii, Leishmania major, and Epstein-Barr virus.

BACKGROUND: Environmental and genetic factors may contribute to the pathogenesis of pemphigus vulgaris (PV) as an autoimmune disease. We aimed to determine rates of seropositivity for immunoglobulin G (IgG) antibodies against a number of infectious agents in untreated and treated PV patients and in healthy individuals. METHODS: Eighty-two newly diagnosed untreated PV patients (34 men and 48 women; mean ± standard deviation [SD] age: 44.18 ± 14.43 years) and 36 previously diagnosed patients under immunosuppressive therapy (16 men and 20 women; mean ± SD age: 38.53 ± 9.96 years) were enrolled in the study. The clinical diagnosis of PV was confirmed by histopathology and direct immunofluorescence findings. As a control group, 131 healthy individuals (68 men and 63 women; mean ± SD age: 42.56 ± 19.69 years) were recruited. In all patients and controls, serum IgG antibodies against Strongyloides stercoralis, Helicobacter pylori, Epstein-Barr virus (EBV) capsid antigen, and Leishmania major were measured using enzyme-linked immunosorbent assays. The indirect immunofluorescence test was used to detect IgG antibodies against Toxoplasma gondii. RESULTS: Newly-diagnosed untreated PV patients had significantly higher rates of seropositivity of IgG antibodies against S. stercoralis and H. pylori compared with the control group (69.5% vs. 16.0% [P < 0.001] and 79.3% vs. 59.5% [P = 0.004], respectively). For the other agents, namely T. gondii, L. major, and EBV capsid antigen, the differences between groups in seropositivity for IgG antibodies were not statistically significant. CONCLUSIONS: Significant associations between S. stercoralis and H. pylori seropositivity rates and untreated disease led to the hypothesis that these pathogenic agents may contribute to the pathogenesis of PV.

Comparison of systemic mycophenolate mofetil with topical clobetasol in lichen planopilaris: a parallel-group, assessor- and analyst-blinded, randomized controlled trial.

INTRODUCTION: Lichen planopilaris (LPP) is the most common cause of inflammatory immune-mediated cicatricial alopecia. If not diagnosed and treated properly, it may lead to irreversible hair loss with a devastating impact on quality of life. However, treatment can be a challenge. In an area lacking these sorts of studies, we conducted a randomized controlled trial (RCT) to study the tolerability and therapeutic effects of topical clobetasol versus systemic mycophenolate mofetil (MMF). METHODS: A randomized, assessor- and analyst-blinded controlled trial was conducted in 60 patients with LPP in Razi Dermatology Hospital, Tehran, Iran, between February and December 2013. Patients were treated with clobetasol lotion 0.05 % applied at night or oral MMF 2 g/day and were followed for 6 months. The Lichen Planopilaris Activity Index (LPPAI) was the primary measure of response to treatment. RESULTS: Systemic MMF and topical clobetasol were equally effective in reducing the LPPAI over 6 months of treatment. Treatment tolerability was excellent in both groups and no serious irreversible adverse effects were detected. Satisfaction with treatment rose in the MMF group over time; however, it declined in the clobetasol group. CONCLUSION: Given the similar efficacy profiles, topical clobetasol seems to be a more suitable and reasonable choice for treatment of LPP than MMF.

Hydroa vacciniforme with eye involvement: report of two cases.

We herein report two patients with hydroa vacciniforme and concomitant ophthalmic involvement, primarily in the form of keratoconjunctivitis leading to corneal opacity. Awareness of this occasional manifestation may help to prevent severe complications.

Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs in association with an underlying neoplasm. Inflammatory myofibroblastic tumour (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated with inflammatory cells, most commonly occurring in the lung. In this study, a case of PNP associated with IMT of the mediastinum is reported. The patient had a favourable outcome following surgical resection and treatment with a systemic steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with sarcomas, specifically IMT, is noteworthy although it is not well studied in the existing literature.

Demographic and histopathologic study of Kaposi's sarcoma in a dermatology clinic in the years of 2006 to 2011.

Kaposi's sarcoma is a low-grade vascular tumor that its prevalence is increasing all around the world due to the increasing prevalence of HIV and organ transplantations. In this study, we assessed risk factors of Kaposi's sarcoma among Iranian patients were referred to Dermatopathology Department of Razi Hospital of Tehran University of Medical Sciences between the years of 2006 to 2011. Also, disease stages have been assessed on pathologic specimens. Thirty four patients diagnosed with Kaposi's sarcoma entered the study. Of the 34 patients, 29% were female, and 71% were male, mean age was 66 years and average disease duration was 6 months. The most common patient's pathologic stages were reported: patch 32%, patch to plaque 24%, plaque 12%. The most prevalent location of involvement was lower extremity (88%), and upper extremity was involved in 24%. At presentation time, the mean number of lesions was 3 to 4. 15% of patients had a history of smoking and 15% had a history of immunosuppressive drugs. HIV infection did not observe in the patients. Based on the present study, Kaposi's sarcoma is a disease of elderly and is higher in older men. The most common site of Kaposi's sarcoma involvement is lower extremity, and the most common pathologic stage was the patch to plaque.

Pemphigus disease activity measurements: pemphigus disease area index, autoimmune bullous skin disorder intensity score, and pemphigus vulgaris activity score.

IMPORTANCE: Recently, the clinical pemphigus disease activity indexes of Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), and Pemphigus Vulgaris Activity Score (PVAS) were validated to correlate with physician global assessment. The antidesmoglein (anti-Dsg) autoantibodies are known to correlate mostly with pemphigus disease activity. The correlation between these indexes and anti-Dsg1 and anti-Dsg3 enzyme-linked immunosorbent assay values has not been previously evaluated. OBJECTIVES: To evaluate the PDAI, ABSIS, and PVAS in a large number of patients with pemphigus vulgaris and to compare the interrater reliability of these indexes and the convergent validity according to anti-Dsg values. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was performed in 2012 in a referral university center for autoimmune bullous diseases. One hundred patients with confirmed diagnoses of pemphigus vulgaris and clinical pemphigus lesions (mean [SD] age, 43.3 [1.7] years; age range, 14-77 years; female-male ratio, 1:3) were studied. Three dermatologists familiar with immunobullous diseases and the indexes rated the patients. INTERVENTIONS: All 100 patients were evaluated with the PDAI, ABSIS, and PVAS. Three dermatologists independently rated all 3 indexes for each of the patients on the same day. Serum anti-Dsg1 and anti-Dsg3 enzyme-linked immunosorbent assay values were measured simultaneously. MAIN OUTCOMES AND MEASURES: Analyses of interrater reliabilities, convergent validities according to anti-Dsg titers, correlation between the distribution and types of lesions with disease activity, predictors of higher titers of antibody (multiple regression analysis), and cutoff values of measures for 2 titers of anti-Dsg with optimal area under the curve, sensitivity, and specificity were performed. RESULTS: The interrater reliabilities were highest for the PDAI, followed by the ABSIS and the PVAS (intraclass correlation coefficients of 0.98 [95% CI, 0.97-0.98], 0.97 [95% CI, 0.96-0.98], and 0.93 [95% CI, 0.90-0.95], respectively). The convergent validity was highest for the PDAI, followed by the PVAS and the ABSIS (Spearman ρ = 0.67, 0.52, and 0.33, respectively). Head, neck, and trunk involvement were predictors of higher titers of anti-Dsg1. CONCLUSIONS AND RELEVANCE: Among the 3 studied indexes, the PDAI had the highest validity and is recommended for use in multicenter studies for rare diseases, such as pemphigus vulgaris.