Persistent Course Research Articles

Congenital cutaneous mastocytosis mistaken for non-accidental injury.

A previously well male infant presented to his general practitioner (GP) for his routine 6-week check. His parents reported the presence of tan-brown lesions since birth. The marks were uniform in color, were present on the trunk, scalp, and face, and were not overlying bony prominences. The GP was concerned that these lesions represented bruising as a manifestation of non-accidental injury (NAI), and arranged an urgent review at our pediatric department. Following assessment by the pediatric team he was admitted for investigation of potential NAI, and dermatology consultation was sought. On examination, scattered reddish brown to tan macules and papules were noted on the torso and limbs, not overlying bony prominences (Figure 1A, B). Darier's sign was negative, although some reactive cutis marmorata was appreciable on the trunk following the rubbing of multiple lesions. A diagnosis of urticaria pigmentosa (UP), now known as maculopapular cutaneous mastocytosis (CM), a form of CM, was made clinically. Skin biopsies demonstrated an infiltrate of spindled and round mast cells and scattered eosinophils within the superficial and mid dermis, with immunohistochemistry positive for CD117, consistent with CM (Figure 1C–E). Blood tests during admission showed a normal complete blood count and coagulation screen (including von Willebrand factor), normal renal and liver function, normal lactate dehydrogenase, normal immunoglobulins, and normal mast cell tryptase. Cranial ultrasound and abdominal ultrasound (including liver and spleen) were normal. Mastocytosis is a spectrum of disease characterized by the pathologic accumulation of mast cells in tissues, including skin, bone marrow, and the gastrointestinal tract. The World Health Organisation has outlined three variants: CM, systemic mastocytosis, and mast cell sarcoma. CM can be further classified as maculopapular CM, also known as UP; diffuse CM; and localized cutaneous mastocytomas.1 Pediatric CM is regarded as a benign condition limited to skin, most commonly presenting as UP, which usually spontaneously regresses in puberty.2 In contrast, adult-onset mastocytosis is more often associated with systemic involvement, a persistent course, and activating mutations of the KIT gene.1 With UP, children typically present in the first two years of life with multiple reddish-brown macules, papules, and/or plaques distributed anywhere on the body, most commonly the trunk. In darkly pigmented skin, lesions may be hyperpigmented and erythema less appreciable. Darier sign, a transient urticarial response upon gentle rubbing of the skin, is classic and supportive of the diagnosis, though not always demonstrable. Treatment with antihistamines can be helpful.3 UP has rarely been reported to be misdiagnosed as NAI.4, 5 Other ‘bruising’ mimics include disorders of coagulation, Valsalva petechiae, vasculitis, acute hemorrhagic edema, incontinentia pigmenti, phytophotodermatitis, coin rubbing, spooning, cupping, Mongolian spots, morphea, neuroblastoma, and ink stains, some of which may be unfamiliar to pediatricians or dermatologists.5 CM can be differentiated from bruising by the typically monomorphic appearance; the persistence of lesions with very gradual resolution; the development of new lesions without trauma; the presence of lesions on any part of the body, not specifically overlying bony prominences; the presence of itch; and the presence of Darier sign. Dermatologists have a crucial role in recognizing cutaneous manifestations of NAI in children, which commonly includes bruising, particularly in infants who are not yet mobile.4 While consideration of NAI is important in all children presenting for medical care, this case highlights the importance of considering underlying dermatoses to avoid unwarranted distress and unnecessary investigations. Written informed consent was obtained from the patient's parent. None.

A case of ruptured Baker's cyst induced by nivolumab and ipilimumab

Here, we presented the rare case of ruptured Baker's cyst induced by immune checkpoint inhibitors (ICIs). The history of more than one immune-related adverse event (irAE) like our case was reported to be associated with a more persistent course of arthritis. Mild persistent inflammation without subjective symptoms might exist after first ICI therapy followed by ruptured Baker's cyst. It is important to pay attention to potential musculoskeletal irAEs in ICI-treated patients with multiple irAEs. Emerging evidences have demonstrated the great efficacy of immune checkpoint inhibitors (ICIs) for various malignancies through enhancing antitumor immune responses. On the contrary, ICIs can cause immune-related adverse effects (irAEs) affecting various organ systems. Here, we report the rare case of ruptured Baker's cyst induced by ICIs. A 50-year-old Japanese woman referred to our department with a 3-month history of the vulvar enlarging nodule. She had no history of musculoskeletal diseases. Clinical examination revealed a 12 × 16 mm-sized black nodule on the right vulva (Figure 1A) and ipsilateral swollen inguinal lymph nodes. The tumor was resected with a 10-mm margin, and the sentinel lymph node biopsy (SLNB) was performed. The resection specimen showed massive invasion of round to oval tumor cells with melanin in the dermis (Figure 1B). The tumor thickness was 2.9 mm, and the SLNB was negative. Positron emission tomography-computed tomography (CT) found no evidence of distant metastasis. The diagnosis of malignant melanoma pT3bN0M0, stage IIB, was made. After surgery, she was followed up without additional treatment. Twenty months later, the metastasis appeared in right inguinal and external iliac lymph nodes (Figure 1C). The combination of nivolumab and ipilimumab every 3 weeks was started. After two courses, enteritis developed and she received oral prednisone 60 mg daily with the cessation of the chemotherapy, although lymph node metastases decreased in size (Figure 1D). During tapering prednisone, she developed pancreatitis, which was relieved by fasting and supplementation. Prednisone was tapered to 5 mg daily 2 months later and the administration of nivolumab alone was resumed. However, 2 days after the single nivolumab use, bilateral knee pain and right knee swelling appeared. Contrast-enhanced CT revealed that low-density areas with a light edge were present in both knees and that the right one extended inferiorly along the gastrocnemius muscle (Figure 1E). Rheumatoid factor and anticyclic citrullinated peptide antibody were negative. She was diagnosed as ruptured Baker's cyst induced by ICIs. The dose of prednisone was increased to 20 mg daily and salazopyrin was added, resulting in the gradual improvement. Although nivolumab was stopped, metastatic lesions have kept the decrease in size for more than 20 months (Figure 1F). Most musculoskeletal irAEs are mild arthralgia, whereas a minority of patients develop inflammatory arthritis (IA) with more pronounced pain.1, 2 In this report, we presented the seronegative IA case presenting as ruptured Baker's cyst during the ICI treatment. Baker's cysts rarely manifest alone and are usually associated with other articular inflammatory conditions.3 The history of more than one irAE like our case is associated with a more persistent course of arthritis.4 Mild persistent inflammation without subjective symptoms might exist after first ICI therapy in our case. There has been one report of ruptured Baker's cyst during the nivolumab treatment.1 Consistent with the above hypothesis, the patient developed occasional self-remitting bilateral knee joint pain preceded by several other irAEs prior to the onset of ruptured Baker's cyst. It is important to pay attention to potential musculoskeletal irAEs in ICI-treated patients with multiple irAEs. The authors declare no conflict of interest. Approval of the research protocol: No human participant was involved in this study. Informed Consent: Informed consent was obtained from the patient. Registry and the Registration No.: N/A. Animal Studies: N/A.

A clinical case of a complicated course of immunoglobulin A vasculitis with long-term nephritis: peculiarities of treatment

Immunoglobulin A vasculitis is the most common systemic vasculitis in children. Its course can be mild, involving only the skin and not requiring medical intervention, as well as severe, recurrent, long-lasting — when the gastrointestinal tract and kidneys are involved. Nephritis is the most often cause the disease severity, although abdominal pain usually affects the well-being of the child. We present a clinical case of immunoglobulin A vasculitis in a 6-year-old girl who had an acute onset with severe abdominal syndrome and vomiting that preceded the appearance of the rash. The use of direct anticoagulants led to gastric bleeding. Treatment with corticosteroids had a positive effect on the abdominal syndrome, but did not prevent the development of kidney injury with hematuria and moderate proteinuria. Nephritis had a stable persistent course. Recurrences of rashes and abdominal pain were observed. Long-term corticosteroid therapy and renoprotection using angiotensin-converting enzyme inhibitors allowed partial control of the disease. The presented clinical case confirms that the course of immunoglobulin A vasculitis can be long, with frequent relapses of skin manifestations, abdominal syndrome, transformation into glomerulonephritis, even in the presence of only moderate hematuria and proteinuria. Skin manifestations and nephritis cannot be always completely controlled by the first-line therapy, which requires a balanced decision regarding the escalation of treatment, taking into account biopsy data, kidney function, and severity of proteinuria. Renoprotection with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can prevent secondary kidney injury. The implementation of European guidelines in the treatment of immunoglobulin A vasculitis, including that associated with nephritis, will allow unifying the approaches to patient management, detecting kidney damage timely and carrying out appropriate treatment measures.

Longitudinal Course of Sleep Disturbance and Relationship With Itch in Adult Atopic Dermatitis in Clinical Practice.

Background: Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients. Methods: A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. Results: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]). Conclusions: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

P855 The impact of the severe financial crisis on drug persistence and disease course in IBD patients in Lebanon

Abstract Background Lebanon is currently going through an unprecedented financial crisis (considered as one of the worst in the world in modern times) that has affected all aspects of everyday life. In particular, the economical crash has significantly crippled the Lebanese healthcare sector, resulting in severe shortages of basic drugs and medications, most of which cannot be produced locally. Patients with chronic diseases including those with Inflammatory Bowel Disease (IBD) have been impacted most given their need for costly and chronic treatment including biologics. Methods We collected data using a 12-question web survey disseminated through social media platforms of the patient organization, I Battle Disease. The questions aimed to explore the patients’ ability to acquire the necessary medications, whether they had to alter or completely stop their treatment, and any resulting complications (forced corticosteroid use, hospitalization, or surgery) it had on the course of their disease. Results 102 patients completed the survey. The patients were nearly evenly split between Crohn’s disease (53%) and ulcerative colitis (47%). Adalimumab was the most commonly used medication before the economic crisis (30%), followed by infliximab (18%), vedolizumab (10%), ustekinumab (8%), and tofacitinib (8%). Azathioprine and 5-ASA monotherapy were used by 8% and 19% of patients respectively. All biologics and small molecules used to be covered fully by third party payors including the National Social Security Fund (38%), the Ministry of Public Health (22%), and private insurance (18%). As a result of the crisis, the majority of patients (69%) declared stopping or interrupting their treatment in the past 3 years, with most (46%) having interrupted treatment for >12 months. 22% of patients reported switching to azathioprine due to issue in access to biologics. Additionally, 69% of patients reported worsening of their condition after stopping treatment, resulting in forced steroid use (36%), switching to another medication (36%), or unscheduled hospital admission (15%). Further, 66% of participants confirmed that they had to purchase their medications from abroad or through a local private vendor using out-of-pocket foreign currencies. Finally, 12% of patients reported that they had to immigrate or seek employment abroad due to difficulty with drug access. Conclusion The recent financial and economic events in Lebanon have imposed significant challenges on patients with IBD, affecting their adherence to therapy and consequently the control of their disease. There is an urgent need for action within the public health context to improve IBD medication availability and accessibility for the Lebanese population.

Expression of scavenger receptors CD163, CD204, and CD206 on macrophages in patients with pulmonary tuberculosis

The aim of the study was to evaluate the expression of scavenger receptors (CD163, CD204, CD206) on macrophages in patients with pulmonary tuberculosis, depending on the clinical form of the disease and sensitivity of the pathogen to anti-tuberculosis drugs.Materials and methods. 64 patients with pulmonary tuberculosis (TB) were examined: 26 patients with disseminated pulmonary tuberculosis (DTB) and 38 patients with infiltrative pulmonary tuberculosis (ITB). Of these, 42 patients secreted Mycobacterium tuberculosis (MBT) sensitive to basic antituberculosis drugs (ATBD), and 22 patients secreted MBT resistant to first-line anti-TB drugs. Material for the study was venous blood. To isolate monocytes from the whole blood in order to transform them into macrophages, Ficoll density gradient centrifugation with a density of 1.077 g / cm3 was used followed by immunomagnetic separation of CD14+ cells. Monocytes were cultured in the X-VIVO 10 medium with gentamicin and phenol red with the addition of macrophage colony-stimulating factor (M-CSF) (5 ng / ml) at a concentration of 1×106 cells / ml with stimulators: interleukin (IL)-4 (10 ng / ml) and interferon (IFN) γ (100 ng / ml). Immunophenotyping of macrophages was performed using monoclonal antibodies to CD163, CD204, and CD206 on the Beckman Coulter CytoFLEX LX Flow Cytometer. The analysis of the obtained data was carried out using the CytExpert 2.0 software. The results were analyzed using statistical methods.Results. Switching the phenotype of macrophages from the M1-like proinflammatory phenotype to M2-like antiinflammatory one contributes to the chronic course of pulmonary TB, dissemination, and persistence of infection. In the present study, we analyzed the features of the expression of CD163, CD204, and CD206 scavenger receptors on macrophages in patients with pulmonary TB. An increase in the number of macrophages carrying markers of the M2 subpopulation (CD163, CD204, and CD206) on their surface was noted, regardless of the clinical form of pulmonary TB and drug resistance of M. tuberculosis.Conclusion. Studying the mechanisms underlying M1 or M2 activation of macrophages is necessary for a deeper understanding of the immunopathogenesis of TB and the role of innate immunity cells in protecting the body from mycobacteria. The analysis of the expression of scavenger receptors CD163, CD204, and CD206 on macrophages allowed to conclude that, in pulmonary TB, especially in patients with drug resistant M. tuberculosis and infiltrative TB, regulatory mechanisms that suppress the activation of innate immunity are implemented together with polarization of macrophage differentiation towards the M2 phenotype. It may be the cause of immune deficiency induced by the pathogen.

A Rare Case of Urethral Tuberculosis

Urethral tuberculosis is a rare disease since the advent of highly effective anti-tuberculosis drugs. The article describes an extremely rare clinical observation of a 34-year-old patient with the transition of tuberculous inflammation from the subcutaneous tissue to the wall of the urethra with intact kidneys. Since the first blood discharge from the urethra, the diagnostic process took 3.5 years, all these years, multiple examinations for tuberculosis were carried out and the results were negative, while the disease progressed. The diagnosis was differentiated between acute purulent anterior subcutaneous paraproctitis and festering pararectal cyst. There were repeated openings of the perineal abscess, no bacterial growth was observed, histological tests revealed chronic purulent inflammation. In view of the persistent recurrent course of perineal abscess, tuberculosis was repeatedly suspected. Acid-resistant mycobacteria were found in the discharge from the fistula by fluorescent microscopy: 10-99 in the sample. Tuberculous mycobacteria were not found in the urine by polymerase chain reaction. The patient was diagnosed with A18.4. Tuberculosis of subcutaneous fat (perineum). Mycobacterium tuberculosis (+). The course of disease was complicated by perineal fistula. With the anti-tuberculosis treatment, the fistulous opening healed within a month.

The role of IL-33 and IL-1β in the development of persistent allergic rhinitis in overweight/obese children

BACKGROUND: Few works were devoted to the study of the role of cytokines in children with allergic rhinitis (AR) with comorbid obesity.
 AIMS: To study the level of cytokines interleukin (IL)1, IL-33, IL-6, tumor necrosis factor (TNF)-, and total IgE in the blood serum of overweight/obese children with intermittent and persistent AR.
 MATERIALS AND METHODS: This cross-sectional observational study analyzed 69 children aged 710 years with AR in the remission period and was conducted from November 2020 to February 2021. All children went through a comprehensive examination for 3 days, including the definition of the serum concentrations IL-1, IL-33, IL-6, TNF-, and total IgE. Before blood sampling, children did not use nasal glucocorticosteroids, antileukotriene drugs for the last 4 weeks, and antihistamines for the last 7 days. Bioimpedansometry was used to assess the body weight by calculating the %FM (percentage of body fat mass).
 RESULTS: The study included 44 children with AR and overweight/obesity (group I) and 25 children with AR and normal body weight (group II). The analysis of AR showed that in group I, intermittent AR was detected in 11 (25.0%) children (subgroup IA), whereas a persistent course was found in 33 children (75.0%) (subgroup IB). In group II, intermittent AR was detected in 13 (52.0%) children (subgroup IIA), whereas persistent AR in 12 children (48.0%) (subgroup IIB). The level of IL-1 in the blood serum was significantly higher in the subgroup IB than in subgroup IA (p=0.009). The concentration of IL-33 in children with persistent AR and obesity was significantly lower than that in children with intermittent AR and obesity (p=0.039). The level of IL-33 in the serum negatively correlated with %FM in group IA (r=-0.6673, p=0.035). The concentration of IL-1 negatively correlated with %FM in group IIB (r=-0,738, p=0,037). The levels of IL-6, TNF, and total IgE in obese children did not depend on the severity of AR.
 CONCLUSIONS: The predictors of persistent AR in children with obesity are a decrease in the level of IL-33 and an increase in IL-1 in the blood serum. The negative correlation between the degree of obesity and IL-33 concentration in children with intermittent AR opens a window of opportunity for the personified management of children with AR and comorbid obesity.

Ихтиоздың сирек кездесетін клиникалық түрі - бір жақтық ихтиозформалы эритродермия: Клиникалық жағдай

Congenital ichthyosis is one of the hereditary dermatoses that develop due to a violation of the keratinization process. The clinical manifestation of ichthyosis is characterized by dryness of the skin during physical examination and scaling of different degrees of clarity. Congenital ichthyosis can be classified as one of the most difficult and urgent problems in the field of dermatology and pediatrics due to the fact that the pathogenesis of this pathology is not fully studied, its persistent course, and the difficulty of achieving positive treatment results.In addition, despite many common features, types of ichthyosis are distinguished based on clinical and histological appearance: simple ichthyosis, recessive X-doubled ichthyosis, classic lamellar ichthyosis, bullous and non-bullous congenital ichthyosiform erythroderma. In all these types of ichthyosis, there is a violation of cellular kinetics and their physiological exfoliation process, resulting in excessive keratinization of the skin in the primary manifestation. During ichthyosis, there is a violation of the barrier function of the skin, loss of water between the epidermis and inability of the skin to retain moisture. In this article, we have shared a patient with these symptoms who was diagnosed with unilateral ichthyosiform erythroderma, one of the rare forms of ichthyosis encountered in our practice. This article is informative for general practitioners, neonatologists, pediatricians, dermatovenerologists and geneticists.

Electrical Status Epilepticus during Sleep: Risk Factors, Clinical Course, and Treatment Approaches

Abstract Background The efforts of clinicians are focused on determining the predictors for electrical status epilepticus in sleep (ESES) manifestation, due to the negative effect of ESES on cognition. Treatment approaches remain a leading problem because of therapeutic resistance. Objective We looked for potential risk factors for ESES manifestation and summarize the clinical course and therapeutic approaches in patients with idiopathic and symptomatic ESES. Patients and Methods We retrospectively reviewed the medical data of 51 children with idiopathic ESES and 20 children with symptomatic ESES. Results We observed an earlier age of seizure onset (p = 0.0002) and a higher percentage of cases with multiple seizures (p < 0.00001) and with postictal paralysis (p < 0.00001) in idiopathic ESES compared with childhood epilepsy with centrotemporal spikes. In the idiopathic ESES, the treatment consisted of corticosteroids in patients with permanent ESES remission and transient remission, levetiracetam (LEV) children with permanent ESES remission and transient, clonazepam (CZP) children with permanent ESES remission and transient, ethosuximide (ESM), and sulthiame. The patients with symptomatic ESES had more unfavorable evolution, as 19 children had persistent or relapsing ESES course. Conclusion We consider the earlier age of seizure onset (below 5 years) and the presence of multiple seizures and postictal paresis as risk factors for ESES manifestation. ESES is characterized by a significant therapeutic resistance, especially in the group of symptomatic cases. Good results are observed with LEV, ESM, CZP, and steroids.

New-Onset Guttate Psoriasis: A Long-Term Follow-Up Study

Background: Guttate psoriasis (GP), a distinct variant of psoriasis, is more common in children and adolescents. The long-term course of these patients has sparsely been examined, with few studies reporting the rates of relapse, persistence, and further development of the psoriasis vulgaris phenotype. Objectives: The objective of this study was to characterize the long-term outcomes of new-onset GP and elucidate the potential factors associated with a persistent disease course. Methods: This was a retrospective cohort study. Patients diagnosed with new-onset GP between 2009 and 2020 with a follow-up period of at least 1 year, were enrolled. The examinees were evaluated by dermatologists. Detailed data retrieved from the examinees’ medical files included demographics, disease characteristics, treatment, and comorbidities. A structured telephone questionnaire was used to determine the current psoriasis status: type, severity, and extent. At the end of follow-up, patients with a persistent disease course, defined as having lesions at least a year after disease onset, were compared with patients in complete remission without further psoriasis symptoms. Results: A total of 120 patients (mean age 28.8 years [±15.2], 58.3% women) with new-onset GP flare were identified. At the end of follow-up period (mean 6.2 years [±3.1]), 49.1% (n = 59) of the patients reported active persistent psoriasis. A switch to the psoriasis vulgaris phenotype occurred in 17.5% (n = 21) of the study cohort. Persistent psoriasis was associated with male sex (OR = 2.1, p < 0.05), multiple disease flares (>3; OR = 9.1, p < 0.001), switch to the vulgaris phenotype (OR = 4.16, p < 0.001), and palmoplantar involvement (OR = 5.2, p < 0.01). Conclusion: A persistent disease course is common among patients with new-onset GP, with most retaining their guttate phenotype throughout the disease course. Persistency was associated with male sex, multiple GP flares, switching to the vulgaris phenotype, and palmoplantar involvement.

Neurofilament light chain: a promising diagnostic biomarker for functional motor disorders.

Functional motor disorders (FMDs) are disabling neurological conditions characterized by abnormal movements which are inconsistent and incongruent with recognized neurological diseases. Aim of this study is to investigate whether FMDs are related to structural axonal damage. Consecutive patients with a definite diagnosis of FMD with no other neurological/psychiatric comorbidities (pure FMDs) and age-matched healthy controls (HCs) were recruited in a tertiary center and demographic/clinical data were collected. Serum neurofilament light chain (NfL) assessment was performed with ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assay. 34 patients with FMDs and 34 HCs were included. NfL levels were similar (p = 0.135) in FMDs (median 8.3pg/mL, range 2-33.7) and HCs (median 6.1pg/mL, range 2.7-15.6). The area under curve (0.606, 95% CI 0.468-0.743) confirmed that NfL concentration was not different in the two groups. NfL values were similar in patients with paroxysmal vs persistent disease course (p = 0.301), and isolated vs combined symptoms (p = 0.537). NfL levels were associated with age (p < 0.0001), but not with disease duration (p = 0.425), number of CNS acting drugs (p = 0.850), or clinical features (p = 0.983). Our preliminary data show that NfL levels are similar in patients with FMDs and HCs, indicating the lack of neuroaxonal damage. These results have relevant pathogenic and clinical implications and suggest that serum NfL may be a promising diagnostic biomarker, potentially useful to differentiate functional vs structural neurological disorders.

Problems of diagnostics of oral lichen planus

Lichen planus is a disease most commonly found in both dermatological and dental practice. The etiology of this dermatosis is not fully understood. As a rule, with lichen planus, the organs of the gastrointestinal tract, cardiovascular, nervous, endocrine and other systems are affected. The disease can develop against the background of strong psychoemotional stress. Differential diagnosis of lichen planus is performed with leukoplakia, autoimmune pemphigus, candidiasis and lupus erythematosus.&#x0D; The authors present their own clinical observation of a patient with a lichen planus of the oral mucosa, in whom a diagnostic error led to the series of unsuccessful hospitalizations, examinations, surgical interventions against the background of a gradual aggravation of the mental state.&#x0D; The interest of this clinical observation is that in the case of diagnosis of lichen planus of the oral mucosa, a complete examination of the skin and all mucous membranes is necessary in order to identify the elements characteristic of this disease. Of particular importance is a biopsy with histological and immunohistochemical examination before the start of therapy. With a prolonged course of the disease, the ineffectiveness of invasive therapies requires timely administration of systemic glucocorticoids to achieve remission. Prolonged and persistent course of lichen planus of the oral mucosa can lead not only to the transformation of the process, but also to the development of psychogenic reactions.&#x0D; The article shows the importance of a tandem between a dermatovenerologist, a dentist and a psychiatrist forthe effective care of patients with lesions of the oral mucosa with lichen planus.

41 Twenty years’ experience with juvenile dermatomyositis among Libyan children

BackgroundJuvenile inflammatory myositis are systemic autoimmune diseases of unknown aetiology that are characterized by inflammation of skeleton, muscles, skin, and internal organs. Studies from different regions have reported different incidence and age at onset suggesting that the clinical and demographic features may differ by race and geographic regions. This study aims to describe the characteristics of disease among Libyan children who have been treated in the main rheumatology unit covering most of the population in LibyaObjectivesTo describe the demographic and clinical features of patients with juvenile dermatomyositisTo determine the outcome of children with juvenile dermatomyositis and factors affecting the outcome.Patients and methodsThis is a retrospective descriptive study conducted by reviewing patient records diagnosed with juvenile dermatomyositis from 5/2000–2/2022.ResultsTwenty-one patients were included, female to male ratio was 6:1. Mean age at disease onset was 7.7 ± 2.8 years and their mean follow-up period was 4.36 ± 3.2 years. Most of the patients (14.7%) presented before 1 month of starting symptoms. Most of the patients (13,0.9%), were diagnosed as dermatomyositis, 2 (9.5%) as polymyositis, 2 (9.5%) as amyopathic myositis, and 4 (19%) as overlap syndrome. Family History of dermatomyositis was positive in 4 (19%) of patients and family history of other autoimmune diseases was positive in 5 (23.8%) patients.Around half of the patients had monocyclic disease course (11, 52.4%), 5 patients (23.8%) had polycyclic disease course and other 5 patients (23.8%) had chronic persistent disease course.MRI proximal muscles and EMG were used for diagnosis in 10 patients (48%) and 16 (76.1%) respectively, and muscle biopsy was used in 2 patients to confirm the diagnosis.One overlap patient had severe lung fibrosis on CT scan chest with restrictive lung disease and 4 patients (19%) had restrictive lung disease with normal CT scan chest.Methyleprednisolone pulses were used in 10 patients (50%) with 3 (15%) who required more than one pulse of intravenous prednisolone. Immunoglobulin was used in 12 (60%) of the patients. All patients needed oral prednisolone and methotrexate was used in 15 (75%) of the patients. Other drugs used were Azathioprine in 3 overlap patients, cyclophosphamide and Mycophenolate mofetil in one patient with overlap syndrome. Hydroxychroroquine was used in 6 (30%) of the patients.In the last visit, 12 patients (60%) were in remission, 7 (58%) of them presented before 1 month of disease onset. Fifty-eight percent of the females and 66.7% of the males were in remission. Five patients (25%) had short stature, 3 (15%) had chronic cutaneous changes, 1 (5%) had arrythmia, 2 (10%) had calcinosis, 2 (10%) had osteoporosis, and one patient died.ConclusionA female predominance was noted with age at presentation comparable to other studies.The most frequent manifestations were skin manifestations and musculoskeletal features were the second most frequent symptoms.Patients has low rate of complications with low rate of calcinosis and mortality and none of them had gastrointestinal manifestations.Males were more likely to be in remission. 41 Table 1summarizes the main clinical features at presentation:FeatureNumber and percentageSkin changes17 (81%)Facial oedema1 (4.8%)Hands and feet oedema1 (4.8%)Fever4 (19%)Generalized fatigability12 (57.1%)Arthritis11 (52.4%)Arthralgia1 (4.8%)Muscle weakness15 (71%)Dysphonia4 (19%)Contractures2 (9.5%)

Folliculitis decalvans: clinical and morphological characteristics (literature review)

Folliculitis decalvans is a rare disease of primary cicatricial alopecias, about 11% of all alopecias of this group. Dermatosis was first described by the French dermatologist Charles-Eugne Quinquaud in 1888 and 1889. In recent decades, the number of publications devoted to the etiopathogenesis, clinical and histological characteristics, as well as approaches to the treatment of folliculitis decalvans has increased.&#x0D; The article presents the results of data analysis on the databases Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, RSCI.&#x0D; The etiopathogenesis of the disease is still unknown. The role of seborrhea and skin colonization by Staphylococcus aureus, as well as impaired local immune response and the presence of a genetic predisposition, have previously been discussed. Folliculitis decalvans is now thought to be a result of persistent disruption of the skin barrier that predisposes to subepidermal invasion by opportunistic microorganisms, including Staphylococcus aureus. Clinical, dermatoscopic (trichoscopic) and histological characteristics of dermatosis are being specified. Its characteristic clinical features are a persistent progressive course, the formation of alopecia foci with a rich red edge, pustules and crusts along the periphery of the alopecia foci, polytrichia and the formation of a dense scar that rises above the surrounding skin. Dermatoscopic characteristics depend on the intensity of the inflammatory process. Specific trichoscopic signs of the disease include follicular pustules, yellow tubular desquamation, yellow crusts, perifollicular erythema, perifollicular hemorrhages, and fine tortuous vessels. Depending on the number of these signs, the degree of inflammation is determined. Histological features of the disease include a massive perifollicular infiltrate, the formation of gaps between the epithelium of the follicles and the surrounding stroma, and in the final stages of the process ― fibrous tracts, diffuse fibrosis in the dermis.&#x0D; The treatment of folliculitis decalvans are antibacterial drugs, it is also possible to treat with courses of topical corticosteroids, antiseptic solutions.&#x0D; We assume that the systematization of information about the etiopathogenesis and approaches to the diagnosis and treatment of folliculitis decalvans will improve the diagnosis among other primary cicatricial alopecia and the choice of the tactics of treating folliculitis decalvans.

Investigating the feasibility and effectiveness of a modular treatment program for children and adolescents with depression and interpersonal problems: study protocol of a quasi-experimental pilot feasibility trial (CBASP@YoungAge)

BackgroundDepression is a serious disorder in childhood and adolescence. Affected children and adolescents show significant impairments in various aspects of life. Studies on the effectiveness or efficacy of psychotherapy in depressed children and adolescents are qualitatively very heterogeneous and reveal small effect sizes. There is thus a need to better tailor psychotherapy approaches to these age groups to improve outcomes like parent-child relationship, symptomatology, or quality of life.To address this gap, we designed a modular, individualized treatment program for children and adolescents based on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) including caregiver involvement.MethodThis quasi-experimental pilot feasibility trial is a phase 1 to phase 2 study investigating the feasibility and effectiveness of CBASP@YoungAge by including an intervention group (CBASP@YoungAge) and a treatment-as-usual control group. The treatment of depressive symptoms as well as interpersonal problems with primary caregivers are the main targets of CBASP@YoungAge. Personalization is ensured concerning the treatment course, caregivers’ involvement, and the patient’s age. The primary outcome relates to two areas: the feasibility of the CBASP@YoungAge treatment program in an outpatient context and a change in patients' depressive symptomatology from before to after treatment. We conduct a brief process evaluation after each session in the intervention group to closely monitor the treatment process and examine feasibility from the therapists' and patients' perspectives and mechanisms of symptom change. In addition, we consider interpersonal behavior between children and caregivers, parenting behavior, and monitor the global-health-index in children and parents as secondary outcomes. Pre-, post-, and follow-up data are evaluated.DiscussionThis is the first study of a modular-based intervention program for children and adolescents with depression and a clear focus on the interpersonal problems between the depressed young patient and her/his caregiver. It will provide important knowledge on the feasibility and effectiveness of the program and potential benefits of including caregivers in psychotherapy. Based on this study’s results, we plan a multicenter, randomized, controlled trial whose long-term aim is to improve the psychotherapeutic care of young patients with depression while preventing persistent courses of depressive disorders.Trial registrationGerman Clinical Trials Register, DRKS (identifier DRKS00023281). Registered 17 November 2020–Retrospectively registered

Mycoplasma pneumoniae Infections and Primary Immune Deficiencies.

Mycoplasma pneumoniae (M. pneumoniae) is one of the leading causes of community-acquired pneumonia in children and is also implicated in a variety of reactive extrapulmonary diseases. Recurrent and/or severe respiratory infections are one of the most frequent manifestations of several types of primary immunodeficiency. Here, we reviewed the medical literature to assess the potential relevance of M. pneumoniae in the infections observed in children affected with combined, humoral, and innate primary immune deficiencies. M. pneumoniae does not result to be epidemiologically prevalent as a cause of pneumonia in children affected by primary immunodeficiencies, but this infection can have a persistent or severe course in this category of patients. Indeed, the active search of M. pneumoniae could be useful and appropriate especially in children with humoral immune deficiencies. Indeed, most cases of M. pneumoniae infection in primary immunodeficiencies are described in patients affected by a/hypo-gammaglobulinemia.

PB1870: COVID - 19 IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: HOSPITAL MORALITY PREDICTORS

Background: Patients with chronic lymphocytic leukemia (CLL), as the disease progresses and the tumor load increases, are characterized by high susceptibility and severe course of viral infections. The depth of immune dysfunction can be influenced by factors such as age, comorbidity, disease status and previous treatment. The detection of SARS-COV2 in this cohort of patients made it possible to analyze the course of COVID-19, as well as to develop a strategy for the disease management of these patients. Aims: To assess the risk factors for the severe course of COVID-19, as well as to identify predictors of hospital mortality. Methods: 179 patients with verified CLL and COVID-19 were followed up by the hematology service of Moscow City Clinical Hospital No.52 (Moscow) from April 21, 2020 to November 31, 2021. Anthropometric, anamnestic, clinical and laboratory data were evaluated, treatment tactics of both CLL and COVID-19 were analyzed in 179 patients (69 women and 110 men, median age - 66 years). A statistical multivariate analysis of hospital mortality, factors of unfavorable prognosis of COVID-19 (complications, humoral response, hospital mortality) was carried out. Results: Age was a significant adverse factor for men: the age of a man from 73 years and more, increases the risk of death of the patient by 3.0 times (p<0.05). For women, age was not a significant adverse factor. Assessment of the effect of comorbidity: patients with 6 or more comorbidity scores according to Charlson have 2.2 times greater risk of death; the presence of cardiovascular diseases increases the risk of death of the patient by 2.3 times. The presence of 1 or more lines of chemotherapy in the anamnesis increased the risk of hospital mortality by 1.5 times. Patients who had previously undergone chemotherapy were treated until the moment of discharge statistically significantly longer than patients who had not undergone antitumor therapy. Relapse/progression of the disease was a factor of unfavorable prognosis for the survival of patients with CLL (mortality was 47% compared to 14.7% in patients in remission). A significant unfavorable prognosis is also the Binnet stage C (p<0.05). A valid factor in the failure of COVID-19 (p<0.05) was ICU therapy and the development of secondary bacterial complications (the use of 2nd-line antibacterial therapy). The assessment of the humoral response in 59 patients shows the presence of an increase in IgG on the 10th-14th days of the disease in 44% of patients, among whom no deaths were detected, 1/3 were vaccinated patients. The absence of a humoral response was a statistically significant adverse outcome factor in 25% of patients (p<0.05). Summary/Conclusion: Progression/recurrence of chronic lymphocytic leukemia is a factor in the severe course of COVID-19, and, as a result, increases the risk of hospital mortality. The absence of a humoral response determines the persistent course of COVID-19 and increases the risk of death by 25%. The study of the course of COVID-19 in patients with CLL allows us to identify key aspects affecting the choice of management tactics for this category of patients: additional booster vaccination (stimulation of the humoral response), early detection (screening) of SARS-COV2 for virus-neutralizing antibodies therapy, timely hospitalization of patients.

Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy

A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in FLG contribute to the development and persistence of food allergies. This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. This study recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population. FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. Using the gold standard for food allergy diagnosis, this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.

An electronic health record (EHR) phenotype algorithm to identify patients with attention deficit hyperactivity disorders (ADHD) and psychiatric comorbidities

BackgroundIn over half of pediatric cases, ADHD presents with comorbidities, and often, it is unclear whether the symptoms causing impairment are due to the comorbidity or the underlying ADHD. Comorbid conditions increase the likelihood for a more severe and persistent course and complicate treatment decisions. Therefore, it is highly important to establish an algorithm that identifies ADHD and comorbidities in order to improve research on ADHD using biorepository and other electronic record data.MethodsIt is feasible to accurately distinguish between ADHD in isolation from ADHD with comorbidities using an electronic algorithm designed to include other psychiatric disorders. We sought to develop an EHR phenotype algorithm to discriminate cases with ADHD in isolation from cases with ADHD with comorbidities more effectively for efficient future searches in large biorepositories. We developed a multi-source algorithm allowing for a more complete view of the patient’s EHR, leveraging the biobank of the Center for Applied Genomics (CAG) at Children’s Hospital of Philadelphia (CHOP). We mined EHRs from 2009 to 2016 using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, medication history and keywords specific to ADHD, and comorbid psychiatric disorders to facilitate genotype-phenotype correlation efforts. Chart abstractions and behavioral surveys added evidence in support of the psychiatric diagnoses. Most notably, the algorithm did not exclude other psychiatric disorders, as is the case in many previous algorithms. Controls lacked psychiatric and other neurological disorders. Participants enrolled in various CAG studies at CHOP and completed a broad informed consent, including consent for prospective analyses of EHRs. We created and validated an EHR-based algorithm to classify ADHD and comorbid psychiatric status in a pediatric healthcare network to be used in future genetic analyses and discovery-based studies.ResultsIn this retrospective case-control study that included data from 51,293 subjects, 5840 ADHD cases were discovered of which 46.1% had ADHD alone and 53.9% had ADHD with psychiatric comorbidities. Our primary study outcome was to examine whether the algorithm could identify and distinguish ADHD exclusive cases from ADHD comorbid cases. The results indicate ICD codes coupled with medication searches revealed the most cases. We discovered ADHD-related keywords did not increase yield. However, we found including ADHD-specific medications increased our number of cases by 21%. Positive predictive values (PPVs) were 95% for ADHD cases and 93% for controls.ConclusionWe established a new algorithm and demonstrated the feasibility of the electronic algorithm approach to accurately diagnose ADHD and comorbid conditions, verifying the efficiency of our large biorepository for further genetic discovery-based analyses.Trial registrationClinicalTrials.gov, NCT02286817. First posted on 10 November 2014. ClinicalTrials.gov, NCT02777931. First posted on 19 May 2016. ClinicalTrials.gov, NCT03006367. First posted on 30 December 2016. ClinicalTrials.gov, NCT02895906. First posted on 12 September 2016.