Uncommon sublingual ulceration in an infant

Sir, An eight-month-old girl was referred to our department with an extensive lingual ulceration. The parents noted that she had habitually bitten her tongue since the release of her first teeth at the age of six months. She was a poor feeder and did not sleep well because of the painful lingual ulceration. There was no family history of developmental disorders or congenital syndromes. Intraoral examination revealed a deep, circular, and extensive ulceration of the whole ventral surface of the tongue with intermittent bleeding in the tongue (Figs. 1a – c). An examination of the rest of the intraoral mucosa revealed that the lower central incisors had recently erupted. However, there were two other ulcerations of the palmar surface of the second and third fingers caused by nocturnal finger biting. Neurological examination noted a lack of pain sensitivity related to peripheral neuropathy diagnosed as congenital insensitivity to pain. Based on the clinical features and the particular site on the ventral surface of the tongue against the lower central incisors and ulcerative lesions of the fingers due to self-biting, the lesion was diagnosed as Riga–Fede disease. Because of the size of the ulceration, significant pain during feeding led to inadequate nutrient intake associated with permanent sleep disturbances. Radical treatment was chosen and the lower central incisors were extracted. Topical corticosteroids were prescribed to help with healing. The term Riga–Fede disease has been used to describe a traumatic ulceration that has occurred on the ventral surface of the tongue in newborn babies and infants. It is most commonly related to neonatal or natal teeth but may also occur in infants after the eruption of the primary lower incisors [1]. This benign ulceration occurs as a result of repetitive mechanical trauma caused to the oral mucosal surfaces by the teeth and is most commonly located on the ventral surface of the tongue against the teeth [1,2]. Riga–Fede disease may reveal an underlying developmental or neurologic disorder, including congenital insensitivities to pain [3]. The case of our patient was associated with congenital insensitivity to pain. Failure to diagnose may lead to dehydration and inadequate nutrient intake in the infant because of the significant pain during feeding. No biopsy is needed. The diagnosis of Riga–Fede disease is based on clinical characteristics [1,2]. Treatment should focus on eliminating the source of trauma. Conservative treatment is attempted at first by grinding the sharp edges of the teeth and placing composite resin in a dome shape or by placing a protective ring. If conservative treatment fails to heal the wounds, radical treatment may be necessary, such as extraction of the teeth [2,3]. We believe that Riga–Fede disease must be recognized by clinicians to avoid misdiagnosis and delayed treatment.

23. ZOE-50 and ZOE-70 Placebo Groups Data Shows that Burden of Pain Associated with Herpes Zoster Interferes with Activities of Daily Living

Background Adults ≥ 50 years of age (YOA) are at increased risk of herpes zoster (HZ), a condition which can cause long-term pain and discomfort. In this analysis, we assessed the burden of pain associated with HZ and its interference with activities of daily living (ADL) in patients ≥ 50 YOA. Methods ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) were phase III, observer-blind, placebo-controlled, 1:1 randomized studies in adults ≥ 50 YOA (ZOE-50) and ≥ 70 YOA (ZOE-70) who received 2 doses of the adjuvanted recombinant zoster vaccine or placebo, 2 months apart. To correctly evaluate HZ pain, the analysis was performed only on the placebo groups data of ZOE-50 (≥ 50 YOA) and pooled ZOE-50/70 (≥ 70 YOA pooled data) in the modified total vaccinated cohort (mTVC, primary population for efficacy analysis) HZ-confirmed cases. HZ pain and interference with ADL was assessed by the Zoster Brief Pain Inventory (ZBPI) instrument completed daily by patients for the first 28 days and then weekly until resolution. Time to resolution of clinically significant pain was analyzed using Kaplan Meier methods. We estimated the cumulative area under curve (AUC) of the ZBPI worst pain score and the ZBPI ADL score up to 182 days post-HZ rash onset. A high AUC reflects a higher severity/longer duration of pain. Results Overall, 254 patients ≥ 50 YOA and 284 patients ≥ 70 YOA were included in the mTVC HZ-confirmed cases for the ZOE-50 and ZOE-70 pooled analysis, respectively. In HZ patients ≥ 50 YOA, 94.6% reported any pain (ZBPI pain score > 0), 87.6% clinically significant pain (ZBPI pain score ≥ 3) and 65.1% severe pain (ZBPI pain score ≥ 7). Similarly, in HZ patients ≥ 70 YOA, 93.2% reported any pain, 90.9% clinically significant pain and 68.4% severe pain. It was estimated that 11.6% and 18.3% of patients aged ≥ 50 and ≥ 70 YOA, respectively, had clinically significant pain 3 months after the onset of HZ. The mean AUC at 182 days was 137.24 (≥ 50 YOA) and 190.68 (≥ 70 YOA), for the ZBPI worst pain score and 92.75 (≥ 50 YOA) and 130.89 (≥ 70 YOA), for the ZBPI ADL score. Conclusion Analysis of data provided by patients with confirmed HZ shows that the burden of HZ pain is high and is associated with interference on patients’ ADL. Funding GlaxoSmithKline Biologicals SA Acknowledgment M Maior/S Hulsmans provided medical writing/editorial support (Modis c/o GSK) Disclosures Eliazar Sabater Cabrera, MSc, GSK (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder) Sean Matthews, MSc, GSK (Independent Contractor) Céline Boutry, PhD, GSK (Employee) Nicolas Lecrenier, Ing, PhD, The GSK group of companies (Employee, Shareholder) Anthony L. Cunningham, F.A.H.M.S., MD, M.B.B.S., B. Med. Sci. (Hons), F.R.A.C.P., F.R.C.P.A., F.A.S.M., GSK group of companies (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)

Reducing pain in children with cancer at home: a feasibility study of the KLIK pain monitor app

Purpose This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home. Methods Children (8–18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0–7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP’s) from the hospital’s Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4–6) or 30 min (scores 7–10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews. Results Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP’s participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP’s followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP’s), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts. Conclusion Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home.

Association between learning and memory problems and health outcomes after blood or marrow transplantation (BMT): A BMT survivor study (BMTSS) report.

12014 Background: Cognitive impairment after BMT for hematologic malignancies typically involves processing speed, attention and working memory. Survivors perceive these deficits as learning and/or memory problems. However, limited information exists regarding learning/memory problems experienced by survivors several years after BMT. We addressed this gap using the BMTSS. Methods: BMTSS is a retrospective cohort study examining long-term outcomes of individuals who survived ≥2y after BMT performed between 1974 and 2014 at three transplant centers. Study participants completed a 255-item questionnaire covering diagnosis by a healthcare provider of health conditions (including learning/memory problems), sociodemographic characteristics, and functional status. We used a nested matched case-control study design. Cases consisted of individuals with learning/memory problems developing after BMT (n = 543). Each case was matched to a BMTSS participant without memory problems (controls: n = 543) using the following criteria: cancer diagnosis, race/ethnicity, type of BMT (allogeneic or autologous), and time from BMT. Multivariable conditional logistic regression analysis was used to identify clinical factors (age at BMT, stem cell source, chronic graft vs. host disease [cGvHD], total body irradiation [TBI], fatigue, pain) and demographic factors (household income, education, sex) associated with learning/memory problems. We also examined the association between learning/memory problems and instrumental activities of daily living (IADL). Analyses were stratified by type of BMT. Results: For all survivors (n = 1,086), mean age at BMT was 40.7y and at study participation was 53.3y (18-85); 47% of the study population was females; 78% were non-Hispanic whites; 31% reported an annual household income < $50k. Primary diagnoses included leukemia (50%), lymphoma (36%), and other (14%); 55% received an allogeneic BMT (36% developed cGvHD); 54% received TBI; and 68% received peripheral blood stem cells. Allogeneic BMT survivors with fatigue (odds ratio [OR] = 2.2, 95% CI, 1.4-3.3; p = 0.001), significant pain (OR = 1.8, 95% CI, 1.1-2.9; p = 0.02) and < college education (OR = 1.6, 95% CI, 1.1-2.5; p = 0.02) had higher odds of reporting learning/memory problems. Autologous BMT survivors exposed to TBI (OR = 2.8, 95% CI, 1.4-5.4; p = 0.003) and reporting significant pain (OR = 1.7, 95% CI, 1.0-2.9; p = 0.05) had higher odds of reporting learning/memory problems. Learning/memory problems were associated with increased odds of impairments in IADL in both autologous (OR = 2.1, 95% CI, 1.1-4.0; p = 0.03) and allogeneic (OR = 2.0, 95% CI, 1.2-3.3; p = 0.01) BMT survivors. Conclusions: Modifiable risk factors, such as fatigue and pain, can be targeted to mitigate the learning/memory problems and improve the functional outcomes of BMT survivors.

AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

Young Woman with Leg Lesions

Case Presentation: The patient was a 33-year-old woman with inflammatory bowel disease presenting for worsening lower leg lesions with significant pain recalcitrant to oral doxycycline. Discussion: Pyoderma gangrenosum is a rare ulcerative skin condition with significant pain that is often associated with other systemic diseases typically treated with immunosuppressive medications aimed at the underlying cause.

Treatment of Chemotherapy-Induced Subungual Pyogenic Granuloma with Topical Timolol Solution

<b><i>Introduction:</i></b> Subungual pyogenic granuloma (PG) can be caused by numerous medications including chemotherapeutic agents. These lesions grow rapidly, oftentimes causing significant pain and bleeding, prompting patients to seek treatment. The management of subungual PG ranges from topical steroids to surgical excision. However, patients with chemotherapy-induced PGs are prone to developing multiple or recurrent lesions. Therefore, finding a therapeutic option that effectively eliminates the tumor and prevents the need for repeated procedural interventions is important. The use of topical β-adrenergic antagonists has been reported to be effective in regressing cutaneous PG. <b><i>Case Presentation:</i></b> In this report, we present a case of chemotherapy-induced subungual PG of the toenail arising in a 62-year-old woman that was successfully treated with topical timolol solution. <b><i>Conclusion:</i></b> This case highlights the promising use of timolol solution for therapeutically challenging PGs, such as those of subungual regions. This option may be particularly useful for individuals who are vulnerable to multiple PGs secondary to chemotherapy who wish to avoid repeated procedural interventions.

Long Term Autograft Harvest Site Pain after Ankle and Hindfoot Arthrodesis

Category: Ankle; Hindfoot; Other Introduction/Purpose: Autologous bone has traditionally been the gold standard for grafting material during foot or ankle arthrodesis. While autograft use has been effective, its harvest does present certain distinctive risks to the patient including persistent harvest site pain. Previous studies have examined harvest site pain, but most have focused on the iliac crest and none provide longer term follow-up. The purpose of this study was to examine long-term (7-10 year) donor site pain from four lower extremity harvest site locations in subjects undergoing autograft harvest for hindfoot or ankle arthrodesis. Methods: All subjects in the control arm of a previously conducted Level 1 clinical trial comparing autologous bone with a synthetic bone graft substitute for hindfoot or ankle arthrodesis were invited back for a single visit at a minimum of 5 years following their initial surgery. Autograft was harvested from either the proximal tibia (51.7%), iliac crest (17.2%), calcaneus (15.5%), distal tibia (6.8%), or other location (8.6%). Harvest site pain, fusion site pain, and weight-bearing pain were evaluated using a 100-point visual analog scale (VAS), with clinically significant pain considered as any score greater than 20 (Todd et al., 1996). Results: Of the 130 subjects receiving autograft in the original trial, 58 returned for assessment at a mean follow-up of 9.0 years (Table 1). The mean harvest site VAS at final follow-up was 4.4 (range, 0.0-97.0) with 37.9% of subjects reporting some level of pain. The percentage of subjects who reported clinically significant pain was 35.7%, 21.4%, 18.2%, 10.5%, 8.9%, and 5.2% at 2, 6, 12, 24, 52 weeks, and final follow-up, respectively. Of those subjects reporting clinically significant pain at final follow-up, two had undergone harvest from the proximal tibial and one from the iliac crest. A significant correlation was found between harvest site pain and both weight-bearing and fusion site pain, but not between harvest site pain and the volume of graft harvested. Conclusion: This study is the first to examine persistence of long-term harvest site pain following autologous bone graft harvest during hindfoot or ankle arthrodesis. Over one-third of patients still reported persistent pain at an average follow-up of 9 years, with 5% experiencing clinically significant pain. The proximal tibia harvest site had the greatest incidence of reported pain. These data suggest that harvesting autologous bone does carry inherent risk of persistent, long-term pain. This factor should be considered when informing patients of procedural risks and when choosing between autograft or graft substitute during arthrodesis surgery. [Table: see text]

AbobotulinumtoxinA in the Management of Hallux Valgus in Adult Patients: Results of a Randomised And Placebo-Controlled Phase 2 Trial

Category: Bunion Introduction/Purpose: Hallux valgus (HV) is a progressive foot deformity affecting nearly 25% of adults, characterized by pain and functional disability, and morphological changes in foot appearance due to progressive lateral deviation of the hallux. HV is initially managed with orthotic interventions, which are often ineffective. Corrective surgery can be efficacious, but is associated with significant pain, long recovery times and, potentially, recurrence. AbobotulinumtoxinA (aboBoNT-A, Dysport®) injections may correct the underlying muscle imbalance (resulting from hypertonia of specific forefoot muscles governing the hallux) thought to cause deformity, thereby reducing pain and disability associated with HV. Therefore, the aim of this phase II, placebo-controlled, parallel-group, multicenter study (NCT03569098) was to evaluate the effect of aboBoNT-A on pain and disability associated with HV in adults. Methods: Patients were randomized (1:1:1) to receive aboBoNT-A 300U, 500U, or placebo in a ≥12-week double-blind (DB) phase, followed by a 24-week open-label (OL) phase (OL Cycle 1, 300U [all patients]; OL Cycle 2, 300U or 500U). Total doses were divided equally into four specific foot muscles involved in hallux function. Eligible patients were aged 18–75 years with an HV angle 15–30° and numeric pain rating scale (NPRS) score of ≥4 (0, no pain; 10, worst possible pain). NPRS score was self-reported for 7 days before baseline and before each post-baseline visit. The primary endpoint was change from baseline in NPRS score (7- day average) before DB Week 8. Two post-hoc endpoints were defined as the percentage of days patients’ NPRS scores were: 1) lower than their lowest NPRS score before baseline; and 2) ≥2 points lower than mean baseline NPRS score. Adverse events (AEs) were monitored throughout the study. Results: No statistically significant differences were observed for aboBoNT-A 300U (n=63) or 500U (n=60) versus placebo (n=63) in NPRS scores at DB Week 8 (least squares mean [standard error]: -1.7 [0.3], -2.4 [0.3], versus -2.0 [0.3], respectively). Scores showed a trend towards pain reduction at Week 12 for aboBoNT-A 500U (-2.4 [0.3]) versus placebo (-1.7 [0.3]; p=0.06). Scores reduced further in OL Cycle 1. Post-hoc analyses showed that patients treated with aboBoNT-A 500U spent significantly more days with reduced pain before DB Week 8 compared with those treated with placebo: analysis 1) 63% versus 38% of days, respectively (p<0.01); analysis 2) 55% versus 37% of days, respectively (p=0.06). Results were similar at DB Week 12 (analysis 1: p<0.01; analysis 2: p=0.02, respectively). No new or unexpected AEs were reported. Conclusion: Although the primary endpoint was not met at Week 8, a trend towards significant pain reduction versus placebo was reported for patients with HV at Week 12 following aboBoNT-A 500U injection. Pain was further reduced with repeat injection. Post-hoc analyses indicate that HV patients spent a greater proportion of time with reduced pain following aboBoNT-A 500U injection compared with placebo. This may be a more clinically relevant assessment of benefit than NPRS score averaged over 7 days. Safety results were in line with the known profile of aboBoNT-A.