Mean Delay In Diagnosis Research Articles

Insights from a 10-year Australasian idiopathic hypersomnia patient data registry study.

Idiopathic hypersomnia (IH) is a disorder of central hypersomnolence that results in excessive daytime sleepiness in the absence of another identifying cause. Case studies from sleep clinic patients may not be a fair representation of the wider IH population. This study aims to better characterize patients diagnosed with IH in Australia and New Zealand using online patient-driven survey data. A retrospective analysis of 686 participants from the Hypersomnolence Australia Patient Data Registry diagnosed with either IH (n = 554), narcolepsy type 1 (NT1, n = 54) or narcolepsy type 2 (NT2, n = 78) between January 2013 and October 2022 was performed. Participants with IH reported additional sleep disorders such as OSA (16.4%) and restless legs syndrome (7.9%) and notable comorbidities included depression (46.2%) and anxiety (50%). There was a mean delay in diagnosis of 10 years in participants with IH, when compared to symptom onset. IH presents with unique but also overlapping symptomatology with NT2, with similar reporting of long daytime naps, unrefreshed sleep and automatic behavior. Modafinil was the most common medication (45.5%) used by participants with IH followed by dexamphetamine (44.2%). Most participants with IH reported receiving physician advice regarding positive lifestyle changes but recommend that newly diagnosed patients be given more advice about medication use. This study demonstrates a delay in IH diagnosis when compared to symptom onset and overlapping features of IH and NT2. It also highlights the heterogeneous presentation of IH and the value of large patient registries in future research.

Osteoarticular hydatid disease: Epidemiological features, diagnosis and treatment

Osteoarticular hydatid disease is a very rare disease. Its diagnosis is challenging and often late because of the nonspecific clinical and radiological features. Through this study, we aim to describe the epidemiological, clinical and radiological features of a series of patients diagnosed with osteoarticular hydatid disease.Ten patients were included. The average age was 40,5 years [25-75]. The onset of symptoms was progressive in all cases with a mean diagnosis delay of 11 months [1-48]. Most frequent locations were spinal (n=7), pelvic (n=3) and costal (n=3). Hydatid serology was positive in seven screened patients. Seven patients underwent surgery and all of them received albendazole postoperatively with an average of 8 monthly courses. Total remission was reported in only one patient. There was no significant difference in the clinical outcome based on the number of albendazole courses.The diagnosis of osteoarticular hydatid disease is often challenging because of its progressive onset and nonspecific clinical signs. Epidemiological setting, immunological screening and imaging features contribute to an earlier diagnosis. Its management requires both surgery and long-term antiparasitic treatment.

The impact of diagnosis delay on European patients with generalised myasthenia gravis.

The objective was to determine the mean duration of diagnosis delay for patients with myasthenia gravis from five European countries and explore the impact of >1 year diagnosis delay. Patients with myasthenia gravis (N = 387) from Europe (France/Germany/Italy/Spain/United Kingdom) and their physicians participated in the Adelphi Real World Myasthenia Gravis Disease Specific Programme™. Diagnosis delay (time from symptom onset to diagnosis) was calculated and characteristics described for patients experiencing >1 year and ≤1 year diagnosis delay. Denominators varied according to outcome as missing data were not imputed. Mean (standard deviation) diagnosis delay was 363.1 (520.9) days, and 27.1% (105 out of 387) of patients experienced diagnosis delay >1 year. Among patients with >1 year and ≤1 year diagnosis delay, respectively, 69.2% (72 out of 104) and 17.4% [45 out of 259] had initially received a different diagnosis (physician-reported); 40.0% (42 out of 105) and 24.1% (68 out of 282) were Myasthenia Gravis Foundation of America class III at the time of the survey (physician-reported); 72.4% (76 out of 105) and 61.3% (173 out of 282) had fatigue (subjective physician reporting from a pre-selected list of symptoms); 30.5% (32 out of 105) and 17.4% (49 out of 282) had anxiety and 21.9% (23 out of 105) and 13.1% (37 out of 282) had depression (both subjective physician reporting from a pre-selected list, Likert-style); and mean (standard deviation) MG-QoL-15r score was 14.4 (5.50) and 12.6 (7.84) (self-reported by N = 43 and N = 74 patients, respectively). More than a quarter of patients with myasthenia gravis experienced diagnosis delay of >1 year. These patients had a different clinical profile with regards to severity, symptoms, comorbidities and MG-QoL-15r score, compared with patients experiencing ≤1 year diagnosis delay.

Visual reconstructions of endometriosis pain: An interdisciplinary visual methodology for illness representation.

Endometriosis is a chronic condition in which tissue resembling the endometrium grows outside of the womb, causing severe chronic pain. Research demonstrates the physical, emotional and quality of life impact on people with endometriosis, but pain is reportedly difficult to communicate, resulting in lengthier diagnosis. This work aimed to gain insight into the value of imagery production as a pain communication strategy through a novel synergy of psychological and linguistic/socio-semiotic approaches. A qualitative, multimodal, participant-generated imagery study. Interpretative phenomenological analysis (IPA) and conceptual metaphor and metonymy analysis were utilized to examine visual representations of endometriosis pain. Data were collected in two focus groups with four and six women, respectively; all with a diagnosis of endometriosis, aged 25-40 years old (M = 34.5, SD = 4.2) and a mean diagnosis delay of 8.4 years (SD = 3.6). The overarching theme across visual representations was 'Pain as Physical Violence' with 'colour as emotional representation', 'texture as sensory qualities' and 'materials as sensation' as sub-themes. These are realized through metaphorical and metonymical relations in both the visual representations as well as the accompanying linguistic representation of the process. This study demonstrates the value of a creative mixed-methodologies approach to capture experiential aspects of pain and its impact that are not verbalized in linguistic accounts alone. This can facilitate a deeper understanding of one's pain, acting as a medium for therapeutic adjustment to occur, while facilitating effective and empathic patient-professional conversations surrounding pain.

X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India

Introduction: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. Methods: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. Results: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. Discussion/Conclusions: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

A Cross-Sectional Study of Quality of Life in Patients Enrolled in the Romanian Hereditary Angioedema Registry.

Hereditary angioedema (HAE) is a rare potentially life-threatening genetic disorder characterized by recurrent episodes of angioedema without wheals that can affect any part of the body. The unpredictability of the attacks and the risk of passing the disease to the offspring result in significant physical and emotional burdens for patients, with a negative impact on quality of life. Data about the health-related quality of life in HAE patients from Romania are scarce. This study aimed to evaluate the disease-specific quality of life in patients with HAE from Romania and to determine associated factors. The study included adult patients with HAE enrolled in the Romanian HAE Registry. Disease-specific quality of life was measured using the Hereditary Angioedema Quality of Life questionnaire, a cross-culturally adapted, internationally validated structured survey. The survey was completed by 94 patients (64.9% females; 35.1% males). The mean age of the participants was 44.9 years (SD 14.1). Most patients (88.3%) had type I HAE and were from urban areas (63.8%). The mean ages at symptom onset and diagnosis were 15.1 (SD 11.1) and 36.1 (SD 14.1) years, respectively. The mean diagnosis delay was 20.5 years (SD 14.2). In the evaluated period, all patients had at least one vial of on-demand treatment at home, and 10 were on long-term prophylaxis treatment. The general and dimensional quality of life scores were slightly above the median values of the reference scales. While the general score was not associated with sex or residence, a statistically significant, negative, weak correlation was detected with diagnostic delay. The results suggest that despite the availability of on-demand treatment for all patients, there is a need for other diagnostic and therapeutic interventions to improve the management of the disease and the quality of life for HAE patients from Romania.

Clinical Spectrum of Hereditary Tyrosinemia Type 1 in a Cohort of Pakistani Children.

Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic metabolite buildup. It manifests in acute, subacute, and chronic forms, with early diagnosis and Nitisinone treatment being vital. The study aims to highlight the different clinical presentations of Hereditary Tyrosinemia type 1 in a cohort of Pakistani children. Retrospective observational study. All patients diagnosed with HT1 at Shifa International Hospital, Islamabad and Pak Emirates Military Hospital, Rawalpindi between 2010 and 2023 were included. Information was collected regarding age, gender, symptoms, physical signs, and laboratory results. The study identified 6 cases of HT1. The average age at presentation was 8 months, with a mean delay in diagnosis of 26.8 months. Males were 4 (66.7%) and 2 (33.3%) were females. All patients had underlying liver disease presenting as abdominal distension with hepatosplenomegaly and accompanying growth failure. Four cases presented with rickets, 2 of which had hypophosphatemic rickets. Urine for succinylacetone was raised in all patients. Alpha fetoprotein was raised but hepatocellular carcinoma was diagnosed in 1 patient only. Low protein diet, and vitamin supplements were used for management. Five of the 6 patients died within 2 years of diagnosis. Delayed referrals and unavailability of Nitisinone are the major challenges in diagnosing and treating HT1 in Pakistan.

Diagnosis and treatment delay in patients with OCD in the United States over the past three decades

Obsessive-compulsive disorder is a mental health disorder that can lead to significant functional impairment and profound disability. Studies have shown that delayed diagnosis and treatment and prolonged duration of illness (DI, onset of symptoms to treatment) led to poorer patient outcomes. The purposes of this study are to investigate whether these time frames have improved over time and to identify reasons for delays. Our main hypothesis was that diagnosis delay, treatment delay, and DI have all improved over the past three decades. We grouped 182 participants into three epochs based on their onset of symptoms (epoch 1: 1992 – 2002, epoch 2: 2003 – 2012, epoch 3: 2013 – 2023). There were statistically significant findings across all epochs for mean diagnosis delay (14.3 years in epoch 1, 10.7 in epoch 2, and 2.0 in epoch 3, p < 0.001) and mean DI (15.6 years in epoch 1, 11.6 in epoch 2, and 2.4 in epoch 3, p < 0.001). Mean treatment delay was significant between epochs 2 (0.9 years) and 3 (0.4 years, p < 0.003). Participants’ responses showed that perceived social stigma, limited access to care, and inability to afford care were statistically significant reasons for diagnosis delay across all epochs (p < 0.05), and limited access to care was a statistically significant reason for treatment delay across all epochs (p < 0.005). These findings demonstrate an ongoing need for timely diagnosis and treatment and improvements in access to and affordability of care in the United States.

Congenital Myasthenic Syndrome: case study from a tertiary care institute of Western India

Objective. To describe clinical characteristics, genetic details and management of patients of congenital myasthenic syndrome. Methods. A retrospective study was carried out from 2020 to 2023. Patient who presented with ptosis, ophthalmoplegia, proximal limb weakness with genetically confirmed mutations for CMS were included in the study. Patients who were positive for Acetylcholine receptor antibody (AChRAb) or Muscle specific kinase (MuSK) antibody or any other antibodies suggestive of acquired myasthenia were excluded from the study. Outcome. 6 genetically proven patients were identified out of which 4 patients had CHRNE mutation, 1 patient had CHRNA1 mutation and 1 patient had Dok7 mutation. Mean delay in diagnosis was 15 years. Patient with Dok 7 mutation responded to salbutamol, 1 patient of CHRNE mutation required combination of pyridostigmine, fluoxetine and salbutamol, rest all patient responded to pyridostigmine. It took 4 weeks for improvement after starting salbutamol in patient with Dok7 mutation. Conclusion. Although rare, CMS is potentially treatable group of disease. Patient presenting with early onset muscular weakness should be evaluated thoroughly and CMS should be considered in presence of eyelid ptosis, ophthalmoplegia and proximal weakness with diurnal fluctuations. RNS and genetic testing are paramount in achieving an early diagnosis.

Insights from a joint pediatric dermatology-gynecology vulvar clinic: A retrospective study.

Pediatric vulvar disease has not been widely explored in the medical literature. Few studies focus on vulvar disease in skin of color. The vulvar disease can be distressing for young patients given the sensitive location, and providers may lack experience in diagnosing and managing vulvar dermatoses. We sought to characterize the conditions seen, diagnostic challenges encountered, and the racial and ethnic factors associated with vulvar diseases in our multidisciplinary pediatric dermatology-gynecology vulvar clinic at Children's National. Medical records of 220 patients who presented to our multidisciplinary pediatric dermatology-gynecology clinic were reviewed retrospectively. Lichen sclerosus (LS) (36%, n = 80), inflammatory vulvitis (11%, n = 23), and vitiligo (9%, n = 19) were the three most frequent conditions observed. These conditions were often misdiagnosed as one another. There was a mean delay in diagnosis after symptom onset in LS patients of 16.43 months. LS, inflammatory vulvitis, and vitiligo are common vulvar diseases among pediatric patients. Accurate diagnosis is important because LS must be treated aggressively to prevent sequelae. Further studies are warranted to help differentiate LS and vitiligo with consideration of skin tone.

Abstract 12480: Characterization of Symptoms and Diagnostic Procedures Prior to Diagnosis Among Patients With Pulmonary Arterial Hypertension in the United States

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease associated with non-specific symptoms, which may lead to diagnosis delays and poor outcomes. Research Question: Which symptoms and diagnostic procedures occur prior to PAH diagnosis and do they vary based on diagnosis delay? Aim: To describe PAH symptoms and diagnostic procedures among patients newly diagnosed with PAH. Methods: Adults with PAH were identified from Optum’s de-identified Clinformatics ® Data Mart Database (2016-2021). Eligible patients had continuous health plan enrollment ≥12 months (mo) before the first recorded PAH-related symptoms (i.e., index date ) and from the index date until the first recorded PAH diagnosis on a medical claim (i.e., study period ). Patients also had ≥1 fill for a PAH treatment and ≥1 right heart catheterization at any time post-index. PAH symptoms and diagnostic procedures were described during the study period, overall, and stratified by time between the index date and first PAH diagnosis (i.e., diagnosis delay ; ≤12 mo, 12–24 mo, and >24 mo). Results: The sample included 538 patients (≤12 mo: N=327; 12–24 mo: N=126; >24 mo: N=85). Mean age was 66 years, 60.6% were female, and mean (range) diagnosis delay was 11.8 (0.0–50.2) mo. During the study period, most patients had ≥2 unique symptoms recorded, but those with longer delay had more fatigue (≤12 mo: 26.6%; 12–24 mo: 55.6%; >24 mo: 54.1%), edema (29.1%; 42.9%; 51.8%), and dizziness (10.1%; 23.0%; 18.8%), among others. Mean delay was shorter when the first symptoms were ascites (4.2 mo) and syncope (6.4 mo) and longer for fatigue (14.2 mo) and dizziness (14.0 mo). On average, patients with longer delay had more diagnostic procedures pre-diagnosis (≤12 mo: 4.3; 12–24 mo: 8.2; >24 mo: 8.7), driven by more electrocardiograms (ECG; 1.9; 4.2; 4.5). Overall, 85.5% of patients had an ECG and 83.5% had a transthoracic echocardiography pre-diagnosis. Conclusions: Symptoms such as fatigue, edema, and dizziness were more common in patients with longer time to diagnosis and these patients had more diagnostic procedures. Greater physician awareness and new screening tools (e.g., predictive algorithms using ECG data) could accelerate PAH diagnosis and treatment aiming at improving patient outcomes.

The effect of uveitis and undiagnosed spondyloarthritis: a systematic review and meta-analysis

Delay diagnosis of spondyloarthritis (SpA) is associated with poor functional ability and quality of life. Uveitis is the most frequent extraarticular manifestation in SpA, and its prevalence increases with longer disease duration. This study examines the effect of uveitis on the disease activity and functional outcome of undiagnosed SpA. We reviewed published and unpublished studies. Data were pooled using the random-effects model; pooled means, and mean differences (MDs) were calculated. In the included 14 studies, disease activity, functional index, and inflammatory markers were measured in 2581 patients with SpA with uveitis and 13,972 without. The pooled mean delay in diagnosis of SpA with uveitis (6.08 years; 95% CI 4.77 to 7.38) was longer than those without (5.41 years; 95% CI 3.94 to 6.89). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was the highest for a delay of 2–5 years (5.60, 95% CI 5.47 to 5.73) and the Bath Ankylosing Spondylitis Functional Index (BASFI) score was the lowest for a delay of < 2 years (2.92, 95% CI 2.48 to 3.37) and gradually increased to delay of > 10 years (4.17, 95% CI 2.93 to 5.41). Patients with SpA with uveitis had higher trend of Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP and BASDAI. The delay to diagnosis was longer in SpA with uveitis, and disease activity was often higher than those without uveitis. Early diagnosis of SpA with timely initiation of an appropriate management plan may reduce the adverse effects of the disease and improve functional ability.

E64 Clinical, radiological, and etiological profile of hip pain in children

Abstract Background Hip pain is a frequent complaint in the pediatric population, in orthopedics, and in rheumatology. In children, the clinical features of hip pain vary widely according to age. This clinical variability represents a diagnosis challenge for clinicians. This study aimed to identify the clinical, paraclinical, and etiological spectrum of hip pain in children. Methods A retrospective, descriptive study was conducted between January 2017 and December 2020. We included children aged under 16 years who were hospitalized in the rheumatology and/or pediatric orthopedics department at Mohamed Kassab orthopedics institute for non-traumatic hip pathology. Clinical, biological, and radiological data were collected from recorded medical files. Missed anamnestic data were collected from parents by telephone call. Results We included 81 children. Male predominance was noted (48 boys and 33 girls). The mean age was 9.9 ± 4.4 years with extremes from 1.3–16 years. Limping was the presenting feature in 84.4% of children, followed by pain (76.5%) and refusal to bear weight (12.3%). The mean time of onset to presentation was 8.8 ± 21.3 months. The mean diagnosis delay was 3.5 ± 15.3 months with extremes from 0 to 10 years. Fifty-four (66.7%) children visited their physician at least once before diagnosis. In clinical examination, fever was found in 12 children, and local inflammatory signs in 2 children. Leg length discrepancy was noted in 13 children, hip joint pain in 47 children, and restricted hip movement in 58 children. Elevation of erythrocyte sedimentation rate was noted in (23/28) of children and elevation of C reactive protein in (14/33) of children. An elevated leucocyte count was present in (10/79) patients. Radiographs showed anomalies in 76.5% of cases and Ultrasonography in 90.9% of cases. The final diagnoses of our sample were: slipped capital femoral epiphysis (37%), juvenile idiopathic arthritis (18.5%), hip dysplasia (14.8%), septic arthritis (12.3%), transient synovitis (8.6%) and tumors (4.9%). The chirurgical approach was conducted in 71.6% of patients. Most children (72.5%) had benign outcomes. Conclusion The diagnosis of pediatric hip pain should always follow a standard algorithm. This starts with taking a detailed history from the patient, if possible, and parents and conducting a thorough clinical examination; imaging and/or blood tests may follow if necessary. Ethics The authors declare that they have no conflict of interest.

Factors associated with the number of months of delaying in multiple sclerosis diagnosis: Comparison of count regression models.

Background: It may take a long time to diagnose multiple sclerosis (MS) since the emergence of primary symptoms. This study aimed to use count regression models to compare their fit and to identify factors affecting delay in the diagnosis of MS. Methods: Data were collected from the Nationwide MS Registry of Iran (NMSRI) for Mazandaran Province, Iran, using census sampling until April 2022. The four models of Poisson regression, negative binomial (NB) regression, zero-inflated Poisson (ZIP) regression, and zero-inflated negative binomial (ZINB) regression were used in this study. Results: In this study on 2894 patients, 74.0% were women, and 8.5% had a family history of MS. The mean ± standard deviation (SD) of the patients' age was 34.96 ± 9.41 years, and the mean delay in diagnosis was 12.32 ± 33.26 months, with a median of 0 (Q1-Q3: 0-9). The NB regression model showed the best performance, and factors, including a history of hospitalization and the year of symptom onset, had significant effects on a delayed diagnosis. Besides, the Expanded Disability Status Scale (EDSS) score was significantly different before and after 2017; it was also associated with sex, type of MS, and history of hospitalization. Conclusion: The mean diagnostic delay and the mean age of MS diagnosis are critical in Mazandaran Province. Patients with MS develop the disease at an early age and are diagnosed with a long delay. The time of symptom onset is a significant factor in the diagnosis of MS, and in recent years, there have been improvements in the diagnostic process.

Osteoid osteomas of the hip: a well-recognized entity with a proclivity for misdiagnosis

ObjectivesThe diagnosis of osteoid osteomas (OO) about the hip can be challenging as presenting symptoms can mimic other, more common, periarticular pathologies. Our aims were to identify the most common misdiagnoses and treatments, mean delay in diagnosis, characteristic imaging features and provide tips for avoiding diagnostic imaging pitfalls for patients with OO of the hip.MethodsWe identified 33 patients (34 tumors) with OO about the hip who were referred for radiofrequency ablation between 1998 and 2020. Imaging studies reviewed included radiographs (n = 29), CT (n = 34), and MRI (n = 26).ResultsThe most common initial diagnoses were femoral neck stress fracture (n = 8), femoroacetabular impingement (FAI) (n = 7), and malignant tumor or infection (n = 4). The mean time from symptom onset to diagnosis of OO was 15 months (range, 0.4–84). The mean time from initial incorrect diagnosis to OO diagnosis was 9 months (range, 0–46).ConclusionsThe diagnosis of OO of the hip is challenging, with up to 70% of cases initially misdiagnosed as a femoral neck stress fracture, FAI, bone tumor, or other joint pathology in our series. Consideration of OO in the differential diagnosis of hip pain in adolescent patients and awareness of the characteristic imaging findings are critical for making an accurate diagnosis.Key Points• The diagnosis of osteoid osteoma of the hip can be challenging, as demonstrated by long delays in time to initial diagnosis and high rates of misdiagnoses which can lead to inappropriate interventions.• Familiarity with the spectrum of imaging features of OO, especially on MRI, is imperative given the increase in the utilization of this modality for the evaluation of young patients with hip pain and FAI.• Consideration of OO in the differential diagnosis of hip pain in adolescent patients and awareness of the characteristic imaging findings, including bone marrow edema and the utility of CT, are critical for making a timely and accurate diagnosis.

(125) Sexual Pain Symptoms in 910 Premenopausal Women with Vulvar Lichen Sclerosus

Abstract Introduction Lichen sclerosus (LS) is an autoimmune inflammatory skin condition primarily affecting the vulva and perianal areas and leading to scarring that can affect sexual function. Most research on symptomatology of LS to date includes predominantly postmenopausal populations and focuses on pruritis, not sexual pain symptoms. Objective This study aims to characterize sexual pain symptoms associated vulvar LS among premenopausal women. Methods A cross-sectional web-based study was conducted in premenopausal women with clinical and/or biopsy-confirmed vulvar LS between the ages of 18-50 years. Participants completed a 28-question survey evaluating demographics, characteristics of symptoms, timing and accuracy of diagnosis, and concomitant autoimmune conditions. Numerical data were expressed as mean +/- standard deviation. Bivariate Pearson correlation was used to determine the relationship between age of symptom onset and time interval to diagnosis. Results Of the 956 responses received, 910 met inclusion criteria. Self-reported ethnicity of the study population was 87% White, 4% Latina or Hispanic, 3% Asian, and 1% Black. The mean age of the population was 36.5 years, ranging from 18-50 years. There was a 4.3-year mean delay in diagnosis, with average age of symptom onset of 27.7 years and average age of diagnosis of 33.2 years. There was an inverse correlation between the age at which symptoms began and the time interval to diagnosis with a Pearson correlation coefficient of -0.509 (t(805)=16.752, p&amp;lt;0.0001). Most prevalent symptoms were vulvar fissures (68%), dyspareunia (68%), tearing with intercourse or vaginal insertion (63%), and labial resorption (61%), with vulvar fissures (49%) and dyspareunia (46%). These symptoms were more common than introital stenosis (34%). Vulvar fissures (41%) and dyspareunia (35%) most often prompted medical attention. Thirty-six percent reported clitoral phimosis and 34% reported decreased clitoral sensation. Only 4% of respondents reported that decreased clitoral sensation prompted medical attention. Over 75% of respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (54%) or bacterial vaginosis (22%). Most common concomitant autoimmune condition reported was hypothyroidism (10%); which was significantly greater than the general population prevalence (2%) (p&amp;lt;0.0001). Post-hoc analysis indicated no statistical difference between biopsy-confirmed and clinically-diagnosed LS across all demographics and responses. Conclusions Vulvar LS affects sexual function in premenopausal women. LS symptoms in premenopausal women include vulvar fissures, dyspareunia, tearing with intercourse or vaginal insertion, and decreased clitoral sensation. Dyspareunia is present is over two-thirds of premenopausal women with vulvar LS, with vulvar fissures and tearing much more common and bothersome than introital stenosis. Patients are less likely to be affected by or seek medical attention for clitoral phimosis, even though it is present in over one-third of those with LS. Vulvar LS should be considered and evaluated in women of all ages presenting with vulvar symptoms. Sexual health and function should be a core outcome measure in LS research and addressed in the evaluation and treatment of this condition. Disclosure No

Clinical features and treatment of activated PI3K-delta syndrome in Peruvian children: A case series

IntroductionActivated phosphoinositide 3-kinase δ (PI3Kδ) syndrome (APDS) is an inborn error of immunity (IEI) caused by a gain-of-function mutation in the PIK3CD gene. It is characterized by recurrent respiratory infections, chronic herpes infections, lymphoproliferation, mucosal lymphoid hyperplasia, enteropathy and immune dysregulation. This condition can be misdiagnosed with other diseases, such as lymphoma or other IEI. Additionally, limited knowledge of APDS in physicians could generate delay in diagnosis, treatment and lead to worse outcomes, especially in developing countries. This study aimed to describe the clinical features and treatment of APDS in Peruvian children evaluated in two centers. MethodsWe retrospectively analyzed data from eight patients with APDS evaluated in the two main Peruvian clinical immunology centers. Demographics, clinical features, laboratory analysis, and treatment data were included. ResultsAll patients were female. At the onset of symptoms and diagnosis, the mean age was 1.4 (SD: 0.98) and 6 (SD: 2.1) years, respectively. The mean delay in diagnosis was 4.5 (SD: 2.7) years. No consanguinity was reported, and only one patient had a family history of IEI. The mortality rate was 25% (2 patients). The main clinical manifestations were lymphadenopathy and hepatomegaly (100%), chronic diarrhea and recurrent pneumonia (87.5%), and splenomegaly (62.5%). All the patients had E1021K mutation. Seven patients (87.5%) had elevated IgG and 50% had elevated IgM. Regarding treatment, all the patients received intravenous immunoglobulin (IVIG), 50% were treated with everolimus and only one patient received hematopoietic stem cell transplantation. ConclusionLymphadenopathy, hepatosplenomegaly, chronic diarrhea, pneumonia, and IVIG treatment were the main features. Our cohort had limited treatment options with calcineurin inhibitors and transplantation and laboratory testing such as lymphocyte population and functional antibody tests. Although genetic testing was done on all the patients, it was supported by international collaboration. Therefore, further studies are needed to evaluate the diagnosis and management impact on patients with APDS in our setting.

A real-world characterization of a cohort with eosinophilic esophagitis: looking for severity biomarkers.

Background. Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of disease severity has not been identified. We aimed to determine if sensitization to airborne and food allergens correlates with disease severity, and to evaluate the association between clinical and laboratory characteristics with the severity of EoE. Methods. Retrospective study of EoE patients observed in a differentiated center, 2009-2021. The association between patients' diagnosis age, disease duration before diagnosis, sensitization to airborne/food allergens, serum total IgE and peripheral blood eosinophil values and severe clinical disease (presence of symptoms with a significant impact on quality of life and/or ≥ 1 hospital admission due to EoE complications, namely severe dysphagia, food impaction or esophageal perforation) and histological severe disease (≥ 55 eos/hpf and/or microabscesses in esophageal biopsies) was evaluated. Results. 92 patients were observed, 83% male, 87% atopic. There was a mean delay in diagnosis of 4 years (range 0-31). 84% had aeroallergen sensitization and 71% food sensitization. Food impaction and dysphagia were the most frequent symptoms, and severe clinical disease was observed in 55%. Histologically, 37% had severity criteria. Patients with severe clinical disease had a significantly longer mean disease duration before diagnosis than patients without severe clinical disease (79 vs 15 months, p = 0.021). Patients who described food impaction were significantly older at time of diagnosis than those who have never had impaction (18 vs 9 years, p less than 0.001). There was no significant association (p less than 0.05) between sensitization, serum total IgE and peripheral blood eosinophil values and clinical or histological severity. Conclusions. An older age at diagnosis and a longer disease duration before diagnosis appear to be useful for predicting EoE clinical severity. Despite having been demonstrated a high prevalence of allergic disease, the presence of sensitization to airborne and/or food allergens do not seem to be useful for predicting clinical or histological severity.

Periods till psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis (according to psoriasis patient registry)

Background. Early detection of psoriatic arthritis in patients with psoriasis remains an unmet medical need. Early diagnosis and treatment initiation in patients with psoriatic arthritis decreases the risk of adverse patient outcomes and improves patients quality of life.&#x0D; Aims. To describe a period between psoriasis and psoriatic arthritis onset and a period between psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis.&#x0D; Materials and methods. Analysis of data from the psoriasis patient registry. Patients aged 18 years and older with an established diagnosis of psoriasis and psoriatic arthritis were included in the analysis. Noninclusion criteria: no data on psoriasis and/or psoriatic arthritis onset (for the period between psoriasis and psoriatic arthritis onset description); no data on psoriatic arthritis onset and/or diagnosis (for the period between psoriatic arthritis onset and diagnosis description).&#x0D; Results. Sample size for the descriptive characteristic of period between psoriasis and psoriatic arthritis onset was 891 patients; sample size for the descriptive characteristic of period between psoriatic arthritis onset and diagnosis was 849 patients.&#x0D; Psoriatic arthritis onset preceeded cutaneous manifestation of psoriasis in 2.5% of patients. Concurrent onset of cutaneous psoriasis and psoriatic arthritis (within one year) had 10.7% of patients. In 86.8% of patients, cutaneous manifestation of psoriasis preceded manifestation of psoriatic arthritis.&#x0D; Exclusively of patients with psoriatic arthritis developed before or concurrently with cutaneous manifestation of psoriasis, the mean duration of period between psoriasis and psoriatic arthritis onset was 13.7 10.3 years, the median [IQR] 12 [619] years.&#x0D; In 24% of patients psoriatic arthritis was diagnosed 1 year and more after its onset. The mean (SD) period from signs and|or symptoms onset till psoriatic arthritis diagnosis was 3.9 5.0 years; median [IQR] was 2 [14.5] years.&#x0D; Conclusions. A diagnostic delay in 24% Russian patients with psoriatic arthritis is one year or more. In this subgroup of patients the mean delay in diagnosis of psoriatic arthritis is about 4 years.

Congenital myasthenic syndromes: A study of 15 cases

AbstractBackgroundCongenital myasthenic syndromes (CMS) are rare inherited heterogeneous disorders of neuromuscular transmission.Aims and methodologyThis study aims to describe clinical and investigative characteristics including genetic aspects of patients with congenital myasthenic syndrome (CMS), in a cohort from western India. Retrospective analysis for the study period of 9 years (−January 2013 to December 2021) was performed. Patients were identified by predefined selection criteria using a combination of clinical, electrophysiological, and genetic studies.ResultsFifteen genetically evaluated CMS patients, 11 females, and 4 males were identified. Ten patients had a history of fatigable ptosis at an early age, whereas all patients had varying degrees of proximal weakness at the time of presentation. The mean age at onset was 16 years and the mean age at final diagnosis was 22 years, thereby representing a mean delay in diagnosis of 6 years. Among the total 13 different genetic mutations identified, 4 are not previously reported. The most common genetic mutations identified were CHRNE gene (in 7 patients) followed by DOK7 gene (in 6 patients), and the remaining 2 patients had mutation in MUSK gene. Roma founder mutation (c.1327delG, p.E443ter) was seen in 5 patients with CHRNE gene. Four patients responded to pyridostigmine alone, 7 patients to salbutamol, whereas 4 patients required a combination of pyridostigmine and salbutamol.ConclusionThis study, carried out in a small cohort of patients, highlights the frequent occurrence of Roma founder mutation in our population, and the predominance of CHRNE and DOK7 gene mutations, points of regional importance. Four novel variants were also identified in the genetic studies carried out.