Frank J. A. van den Hoogen

2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

OBJECTIVE The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynauds phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative

Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynauds phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

Effect of Botulinum Toxin in the Treatment of Drooling: A Controlled Clinical Trial

Objective. To investigate the clinical effectiveness of botulinum neurotoxin type A (BoNT) to reduce drooling in children with cerebral palsy (CP). Methods. A controlled clinical trial was performed in which the results of single-dose BoNT injections in the submandibular glands were compared with treatment with scopolamine. Forty-five children who had CP and experienced severe drooling were enrolled. Drooling severity was measured at baseline, during application of scopolamine, and at different intervals after BoNT injections up to 24 weeks, using the Drooling Quotient (DQ), the Teacher Drooling Scale (TDS), and Visual Analog Scales (VAS). Results. Drooling was reduced during scopolamine application as well as after BoNT injections. Compared with baseline, the mean DQ showed a significant decrease throughout the study. Greatest reductions were achieved 2 to 8 weeks after BoNT injection. No significant differences were found between scopolamine measurements and those up to 24 months after BoNT injection. Using VAS, parents recorded the effect on drooling in which significant differences were found between baseline VAS score and all follow-up assessments. According to our definition of “success to therapy,” demanding a 2-point decrease on the TDS, 61.5% of patients responded to BoNT injections. Analysis of the DQ demonstrated a response rate of 53% of the patients to scopolamine and 48.7% to BoNT until 24 weeks after BoNT injections, the actual duration of this study. As a reaction to scopolamine, 71.1% of the patients had moderate to severe side effects. Only nonsevere, incidental side effects were reported after BoNT injections. Conclusions. During scopolamine application as well as after intraglandular BoNT injections, a clinically relevant reduction in drooling was achieved in children with CP, demonstrating maximum effect 2 to 8 weeks after injections. This is the first controlled clinical trial that confirmed a significant effect of BoNT injections in the treatment of drooling. General anesthesia was needed for all children. BoNT injections show fewer and less serious side effects than transdermal scopolamine treatment.

Botulinum toxin A: a new option for treatment of drooling in children with cerebral palsy. Presentation of a case series.

Abstract Drooling beyond the age of 4 years is pathological, particularly if it occurs in children with neurological and developmental impairment and disability. Considering the therapeutic spectrum of botulinum toxin A and in view of the innervation of the salivary glands, we postulated that intraglandular injections into the submandibular glands with botulinum toxin A could reduce the secretion of saliva and consequently decrease drooling. Three patients with cerebral palsy and severe drooling were selected and evaluated over a 4-month period. Under ultrasound guidance, one dose of botulinum toxin A was injected bilaterally into the submandibular glands. Saliva secretion was measured at baseline and repeated four times during the following 4 months. In the three patients, maximal salivary flow rate of the sublingual and submandibular glands was reduced by 51% to 63%. The time of the maximal effect differed among the three children. The parents reported a satisfactory reduction of drooling throughout the whole study period. No objectionable disturbances of oral functions were observed. There was mild transient thickening of saliva in one of the patients. Conclusion The application of botulinum toxin A to the submandibular gland is a promising technique to reduce salivary flow rate and probably an alternative in the treatment of drooling in children with cerebral palsy.

Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

OBJECTIVE To examine the effect of sildenafil in patients with Raynauds phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc). METHODS In this double-blind, placebo-controlled study, 57 patients with RP secondary to lcSSc were randomized to receive modified-release sildenafil 100 mg once daily for 3 days followed by modified-release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week in the per-protocol population. Secondary end points included Raynauds Condition Score, duration of attacks, RP pain score, endothelial dysfunction assessed by a peripheral arterial tonometric (PAT) device, and serum biomarker levels. RESULTS The mean percentage reduction from baseline to day 28 in attacks per week was greater for modified-release sildenafil than for placebo (-44.0% versus -18.1%, P = 0.034); the mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified-release sildenafil treatment (P = 0.244). Decreases from baseline in Raynauds Condition Score, duration of attacks, and RP pain score were not significantly different between groups. Mean values and changes from baseline in PAT responses and serum biomarker levels were similar between groups. The most frequent adverse events were headache and dyspepsia; the majority of adverse events were mild or moderate. CONCLUSION Our findings indicate that modified-release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated. Modified-release sildenafil may be a treatment option in this patient population.

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynauds phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

Validation of potential classification criteria for systemic sclerosis.

Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the face, discriminant, and construct validity of the items to be further studied as potential criteria.

Tracheostomy for long-term ventilated patients: a postal survey of ICU practice in The Netherlands

ObjectiveTo assess the frequency, timing, technique, and follow-up of tracheostomy for long-term ventilated patients in different intensive care units (ICUs) in The Netherlands.Design and settingPostal questionnaire, survey on retrospective data. A questionnaire was sent to all (n=63) ICUs with six or more beds suitable for mechanical ventilation and officially recognized by The Netherlands Intensive Care Society. Pediatric ICUs were excluded.Measurements and resultsThere was an 87% (n=55) response rate of contacted ICUs. The number of tracheostomies per year per unit varied widely (range 1–75), most ICUs (42%) performing between 11 and 25 tracheostomies per year. In 44% of ICUs (n=24) tracheostomy was not performed on a routine basis. In 25% of ICUs (n=14) tracheostomies were performed during the second week of ventilation. Surgical tracheostomy and percutaneous procedures were technique of first choice in 38% and 62% of ICUs, respectively. In only 7% of units were late follow-up protocols in use. Thirty-two units (58%) reported a total of 56 major complications.ConclusionsTiming and technique of tracheostomy varies widely in Dutch ICUs. The percutaneous technique is the procedure of choice for tracheostomy in most of these units. Late follow-up protocols are rarely in use.

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

Aim  To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation.

Supraomohyoid neck dissection with frozen section biopsy as a staging procedure in the clinically node-negative neck in carcinoma of the oral cavity

A retrospective analysis was performed to evaluate the efficacy of elective supraomohyoid neck dissection in 57 newly diagnosed patients with squamous cell carcinoma of the oral cavity. The protocol included sampling of both the most suspicious and the largest node in the jugulodigastric region (if present) and the most distal jugulo-omohyoid lymph node (if present) for frozen section examination. In 10 cases, frozen section biopsy revealed metastatic disease, and surgery was continued using standard or modified radical neck dissection en bloc with the primary tumor. In another 10 cases, histologic examination of the supraomohyoid neck dissection specimens revealed occult nodal disease at other sites. In the histologically proven absence of metastatic disease in the supraomohyoid neck dissection specimens, disease recurrence in the neck occurred in only three cases (7%), all in the presence of local failure. The results of our analysis support the conclusion that elective supraomohyoid neck dissection with frozen section biopsy appears to be a valid staging procedure and a valuable approach to the management of the clinically node-negative neck in squamous cell carcinoma of the oral cavity.