Elaine Siegfried

Etanercept treatment for children and adolescents with plaque psoriasis.

BACKGROUND Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis. METHODS In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physicians global assessment of clear or almost clear of disease, and safety assessments. RESULTS At week 12, 57% of patients receiving etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physicians global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001). At week 36, after 24 weeks of open-label etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label etanercept; all resolved without sequelae. CONCLUSIONS Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819 [ClinicalTrials.gov].).

Timolol Maleate 0.5% or 0.1% Gel‐Forming Solution for Infantile Hemangiomas: A Retrospective, Multicenter, Cohort Study

Abstract:  Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta‐blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel‐forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel‐forming solution and had photographic documentation of the IH and at least one follow‐up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel‐forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63–7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.

Association of facial hemangiomas with Dandy-Walker and other posterior fossa malformations

Cutaneous hemangiomas are common benign tumors of infancy that only rarely are associated with malformations in other tissues or organs. We report nine infants with large facial hemangiomas who also had Dandy-Walker malformations or similar posterior fossa abnormalities. On the basis of the experience with our patients and with those previously reported, we recommend radiographic imaging studies of the brain of infants with large, aggressive facial hemangiomas to rule out posterior fossa defects.

Nephrogenic fibrosing dermopathy: two pediatric cases

We report two pediatric cases of nephrogenic fibrosing dermopathy (NFD), first described in 2000. NFD is a condition in which individuals with renal dysfunction have development of extensive skin hardening and histopathologic evidence of a scleromyxedema-like condition.

The natural history of condyloma in children

BACKGROUND Condyloma acuminatum, an infection caused by human papillomavirus (HPV), has become one of the most common sexually transmitted diseases. Correspondingly, anogenital warts are more frequently diagnosed in children. Twenty-five years ago a landmark prospective study showed that untreated common cutaneous warts in children spontaneously regress within 2 years in two thirds of cases, but a similar study of condyloma has not been published. Several treatment options are available for condyloma in adults; none have been studied or approved by the US Food and Drug Administration for treatment of children. OBJECTIVE Our purpose was to review a cohort of children with condyloma to determine the natural history. METHODS Of 75 originally identified subjects with condyloma, 41 qualified for further retrospective or prospective evaluation, including distribution of lesions, duration of disease, gender, and treatment, if any. RESULTS Overall, condylomas in 31 of 41 children (76%) experienced resolution. Spontaneous resolution occurred within 5 years in 22 of 41 subjects (54%), including 6 of 8 (75%) who never received treatment, and 16 of 33 (49%) in whom treatment failed. In 9 of 33 treated children (27%), resolution occurred during treatment. Girls presented three times more often than boys and resolution occurred comparatively more often in girls. CONCLUSION Spontaneous resolution of pediatric condyloma occurred in more than half of our subjects. Nonintervention is a reasonable initial approach to managing venereal warts in children.

Long-term etanercept in pediatric patients with plaque psoriasis

BACKGROUND No systemic therapies are approved by the US Food and Drug Administration for the treatment of psoriasis in children and adolescents. OBJECTIVE We sought to evaluate the long-term safety and efficacy of etanercept in pediatric patients (aged 4-17 years) with moderate to severe plaque psoriasis. METHODS Patients who completed or received substantial treatment benefit in a 48-week, randomized, double-blind, placebo-controlled study (N = 211) evaluating the efficacy and safety of once-weekly etanercept (0.8 mg/kg) were enrolled in this 264-week open-label extension study. The primary end point was the occurrence of adverse events. Secondary end points included Psoriasis Area and Severity Index 50%, 75%, and 90% responses compared with baseline; static Physician Global Assessment; and clear and clear/almost clear static Physician Global Assessment status. Results from a 96-week interim analysis are presented. RESULTS Of 182 enrolled patients, 181 received treatment and 140 (76.9%) completed week 96. A total of 145 patients (80.1%) reported adverse events; 5 serious adverse events occurred in 3 patients, none of which were treatment related. Observed Psoriasis Area and Severity Index 50% (89%), 75% (61%), and 90% (30%) responses compared with baseline at week 96 were similar to those observed in the double-blind trial. The static Physician Global Assessment was maintained through week 96, when 47% of patients achieved clear/almost clear status. LIMITATIONS This is an interim analysis from an open-label study. CONCLUSION Extended treatment with etanercept in pediatric patients with moderate to severe plaque psoriasis was generally well tolerated, and efficacy was maintained through 96 weeks.

Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum.

Abstract Objective. To describe unusual clinical and radiological features in patients with chronic recurrent multifocal osteomyelitis (CRMO). Design and subjects. Based on radiographic and microscopic findings, three patients were prospectively diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form the basis of this report because of either the unusualness of the clinical presentation, hitherto undescribed associated diseases or the unusual age of presentation and sites of lesions. Results. One patient developed pyoderma gangrenosum at the site of one of the skeletal lesions and then went on to develop ulcerative proctitis. A second patient presented with a soft tissue mass, which on MRI mimicked a sarcoma. The final patient presented with lesions in the wrist and phalanges of the toes at the unusual age of 38. None of the patients was treated with steroids or antibiotics for the skeletal lesions. Steroids were administered to one patient for treatment of pyoderma gangrenosum. Conclusions. The pattern and distribution of skeletal lesions in CRMO are well recognized in the pediatric age group. The unusual clinical and/or radiological features discussed herein suggests that this is a disease that continues to evolve with a broader spectrum of features than recognized.

Chronic recurrent multifocal osteomyelitis preceding pyoderma gangrenosum and occult ulcerative colitis in a pediatric patient.

Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is a clinicopathologic entity of unknown origin mainly affecting children and young adults. It shares many clinical features with pyoderma gangrenosum (PG), an uncommon ulcerating inflammatory disorder of the dermis and underlying subcutaneous fat. Both conditions are chronic and relapsing, and have been associated with inflammatory bowel disease (IBD). The diagnoses are made by exclusion. Histology is nonspecific and cultures are negative. There has been only one previous report of both conditions occurring in the same patient. Here we describe the second case, a 12‐year‐old girl who developed pyoderma gangrenosum in direct continuity to an underlying CRMO lesion of the right anterior tibia. Occult ulcerative colitis (UC) was subsequently discovered.

Subcutaneous efalizumab is not effective in the treatment of alopecia areata

BACKGROUND Alopecia areata (AA) is a T-cell-mediated autoimmune disease. Efalizumab is a T-cell-targeted therapy approved for the treatment of psoriasis. OBJECTIVE To assess the efficacy and safety of efalizumab in the treatment of moderate-to-severe AA. METHODS Sixty-two patients were enrolled into this phase II, placebo-controlled trial. The trial consisted of three 12-week periods-a double-blind treatment period, an open-label efalizumab treatment period, and a safety follow-up. RESULTS There were no statistical differences between treatment groups in percent hair regrowth, quality-of-life measures, or changes in biologic markers of disease severity after 12 or 24 weeks. In both groups, there was an approximately 8% response rate for hair regrowth (at 12 weeks). Efalizumab was well tolerated. LIMITATIONS Numbers were too small for certain analyses. CONCLUSION A 3- to 6-month trial of efalizumab was not effective in promoting hair regrowth in this small cohort of patients with moderate-to-severe AA.

Cimetidine therapy for recalcitrant warts in adults: Is it any better than placebo?

Three open-label, uncontrolled studies have documented successful treatment of warts with cimetidine, whereas two placebo-controlled, double-blind studies and two open-label comparative trials have failed to demonstrate efficacy. This double-blind, placebo-controlled study was designed with stringent enrollment and outcome criteria to minimize the confounding issue of spontaneous remission. Efficacy was not statistically superior to that of placebo, but a trend toward efficacy was suggested for younger subjects.