A Retrospective Analysis of Efficacy and Safety of Intralesional Triamcinolone Injections in the Treatment of Frontal Fibrosing Alopecia Either as Monotherapy or as a Concomitant Therapy.

CONTEXT: Frontal fibrosing alopecia (FFA) is a primary cicatricial alopecia characterized by progressive recession of frontal, and often temporoparietal, hairline mainly in postmenopausal women. Currently, there are no guidelines or proposed evidence-based treatment for FFA. AIMS: The aim of this study was to retrospectively evaluate the effect and safety of intralesional triamcinolone acetonide injections (ITAIs) either as monotherapy or as concomitant treatment in the management of hairline recession in FFA. SUBJECTS AND METHODS: All patients with FFA, who visited our specialist hair clinic from July 2012 to October 2016 and were treated with ITAI either as monotherapy or as concomitant treatment, were enrolled in our study. Measurements were performed from five different points on the scalp. The analysis of data included demographics, associated symptoms, clinical and dermoscopic findings, comorbidities, family history of FFA, concomitant medication, treatment outcome, and recording of adverse events. STATISTICAL ANALYSIS: Statistical analysis was performed using the Statistical Package for the Social Sciences, version 22.0. RESULTS: A total of 40 patients, all females were enrolled in our study. The mean age of the patients was 65.88 ± 8.18 whereas the mean age of the diagnosis was 61.24 ± 7.4. A total of 39 patients were treated with a combination of treatments, including ITAI, and only one with ITAI as monotherapy. There was a halting of the progress of the disease, and no significant adverse events were noted, apart from mild pain. CONCLUSIONS: A halting in the progression of FFA was achieved, with unremarkable adverse events. ITAI could serve as an effective and safe option for the treatment of FFA, although difficult to assess it as monotherapy. Further randomized controlled trials are needed to evaluate its efficacy and safety as the sole treatment in the management of FFA.

Pharmacoeconomics of PCSK9 inhibitors in 103 hypercholesterolemic patients referred for diagnosis and treatment to a cholesterol treatment center.

BACKGROUND: PCSK9 inhibitor therapy has been approved by the FDA as an adjunct to diet-maximal tolerated cholesterol lowering drug therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) with suboptimal LDL cholesterol (LDLC) lowering despite maximal diet-drug therapy. With an estimated ~24million of US hypercholesterolemic patients potentially eligible for PCSK9 inhibitors, costing ~ $14,300/patient/year, it is important to assess health-care savings arising from PCSK9 inhibitors vs ASCVD cost. METHODS: In 103 patients with HeFH, and/or ASCVD and/or suboptimal LDLC lowering despite maximally tolerated diet-drug therapy, we assessed pharmacoeconomics of PCSK9 inhibitor therapy with lowering of LDLC. For HeFH diagnosis, we applied Simon Broome's or WHO Dutch Lipid Criteria (score >8). Estimates of direct and indirect costs for ASCVD events were calculated using American Heart Association (AHA), U.S. DHHS, Healthcare Bluebook, and BMC Health Services Research databases. We used the ACC/AHA 10-year ASCVD risk calculator to estimate 10-year ASCVD risk and estimated corresponding direct and indirect costs. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors, we calculated direct and indirect health-care savings. RESULTS: We started 103 patients (58 [56 %] women and 45 [44 %] men), on either alirocumab (62 %) or evolocumab (38 %), median age 63, BMI 29.0, and LDLC 149 mg/dl. Of the 103 patients, 28 had both HeFH and ASCVD, 33 with only ASCVD, 33 with only HeFH, and 9 had neither. Of the 103 patients, 61 had a first ASCVD event at median age 55 and on best tolerated cholesterol-lowering therapy median LDLC was 137 mg/dl. In these 61 patients, total direct costs attributable to ASCVD were $8,904,361 ($4,328,623 direct, $4,575,738 indirect), the median 10-year risk of a new CVD event was calculated to be 13.1 % with total cost $1,654,758. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors in our 61 patients, $4,452,180 would have been saved in the past; and future 10-year savings would be $1,123,345. CONCLUSION: In the 61 CVD patients, net costs/patient/year were estimated to be $7,000 in the past, with future 10-year intervention net costs/patient/year being $12,459, both below the $50,000/year quality adjusted life-year gained by PCSK9 inhibitor therapy.

Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis.

Although this effect is not widely recognized, testosterone therapy can interact with thrombophilia, causing osteonecrosis. In 12 men and 4 women who had idiopathic osteonecrosis a median of 6 months after the onset of testosterone therapy, the authors examined the interaction between testosterone therapy and previously undiagnosed thrombophilia. The authors hypothesized that patients who had osteonecrosis after starting testosterone therapy were more likely than 110 normal control subjects or 48 patients who had osteonecrosis and were not receiving testosterone therapy to have thrombophilia. Measures of thrombophilia included Factor V Leiden, prothrombin, PAI-1 gene mutations, Factor VIII, Factor XI, anticardiolipin antibody immunoglobulin G or immunoglobulin M, and homocysteine values. In 10 cases, osteonecrosis occurred 6 months or less after the onset of testosterone therapy, and in all 16 cases, it occurred after a median of 6 months of testosterone therapy. Of the 16 cases, 5 (31%) were Factor V Leiden heterozygotes vs 2 of 109 (2%) healthy control subjects (P=.0003) and 4 of 48 patients who had osteonecrosis and were not receiving testosterone therapy (P=.04). Of the 16 cases, 4 (25%) had high (>150%) Factor VIII levels vs 7 of 103 (7%) healthy control subjects (P=.04), and 3 (19%) had high (>150%) Factor XI levels vs 3 of 101 (3%) healthy control subjects (P=.03). Of the 16 patients with osteonecrosis, 14 (88%) had at least 1 abnormal procoagulant value (of the 8 measured) vs 47 of 110 (43%) healthy control subjects (P=.0009). Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (≥42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis.

Testosterone, thrombophilia, thrombosis.

We screened previously undiagnosed thrombophilia (V Leiden-prothrombin mutations, Factors VIII and XI, homocysteine, and antiphospholipid antibody [APL] syndrome) in 15 men and 2 women with venous thromboembolism (VTE) or osteonecrosis 7 months (median) after starting testosterone therapy (TT), gel (30-50 mg/d), intramuscular (100-400 mg/wk), or human chorionic gonadotropin (HCG) (6000 IU/wk). Thrombophilia was studied in 2 healthy control groups without thrombosis (97 normal controls, 31 subjects on TT) and in a third control group (n = 22) with VTE, not on TT. Of the 17 cases, 76% had ≥1 thrombophilia vs 19% of 97 normal controls (P < 0.0001), vs 29% of 31 TT controls (P = 0.002). Cases differed from normal controls by Factor V Leiden (12% vs 0%, P = 0.021), by high Factor VIII (>150%) (24% vs 7%, P = 0.058), by high homocysteine (29% vs 5%, P = 0.007), and from both normal and TT controls for APL syndrome (18% vs 2%, P = 0.023, vs 0%, P = 0.04). Despite adequate anticoagulation with TT continued after the first deep venous thrombosis-pulmonary embolus (DVT-PE), 1 man sustained 3 DVT-PEs 5, 8, and 11 months later and a second man had 2 DVT-PEs 1 and 2 months later. Of the 10 cases with serum T measured on TT, 6 (60%) had supranormal T (>800 ng/dL) and of 9 with estradiol measured on TT, 7 (78%) had supranormal levels (>42.6 pg/mL). TT interacts with thrombophilia leading to thrombosis. TT continuation in thrombophilic men is contraindicated because of recurrent thrombi despite anticoagulation. Screening for thrombophilia before starting TT should identify subjects at high risk for VTE with an adverse the risk to benefit ratio for TT.