Concomitant Autoimmune Diseases Research Articles

Concomitant autoimmunity and risk of multiple sclerosis disability worsening

BackgroundFew studies have examined the effect of concomitant autoimmune diseases on multiple sclerosis (MS) disability worsening. We set out to examine whether concomitant Crohn's Disease (CD), Ulcerative Colitis (UC), or Type 1 Diabetes (T1D) affect MS disability worsening in a nationwide cohort of MS patients as defined by reaching expanded disability scale status (EDSS) scores 3.0, 4.0 and 6.0. MethodsPatients with MS onset between January 2004 and January 2019 were identified from the Swedish MS registry and the Swedish National Patient Register. Kaplan–Meier analysis was used to estimate the median time to reach sustained disability milestones. Adjusted Cox proportional hazard regression models were used to calculate the risk of reaching disability milestones among persons with and without CD, UC, or T1D. ResultsOut of 8972 persons with MS, 88 (1.0 %) had T1D, 47 (0.8 %) had UC, and 78 (0.9 %) had CD. There was a significantly higher risk of disability progression, for persons with MS and T1D for reaching EDSS 6.0, hazard ratio (HR) = 2.21 (95 % confidence interval (CI) = 1.48 −3.31) and persons with MS and comorbid CD for reaching EDSS 3.0, HR = 2.30 (95 %CI = 1.74–3.04) and 4.0, HR = 1.59 (95 %CI = 1.09–2.32), and persons with MS and comorbid UC for reaching EDSS 3.0 HR = 1.57 (95 %CI = 1.15–2.14). As defined by Charlson's comorbidity index, the co-existence of other co-morbidities conferred a significant increase in the risk of reaching all endpoints, with HR ranging from 1.23 to 1.62. ConclusionComorbidity is associated with a significantly increased risk of reaching disability end-points, and T1D, CD, and UC increase the risk further. Thus, there appears to be a need for increased vigilance of comorbidites in persons with MS in order to optimise the long-term outcome of MS.

OA14 Subcutaneous panniculitis-like T-cell lymphoma: a mimic of lupus erythematous panniculitis

Abstract Background/Aims Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus characterised by tender, erythematous subcutaneous nodules or plaques on the face, trunk and proximal extremities. Without treatment, profound lipoatrophy frequently occurs, which often has a devastating psychosocial impact. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous T-cell lymphoma, which may appear in a similar manner. SPTCL initially preferentially infiltrates the subcutaneous adipose tissue and symptoms vary widely depending on the stage of the disease. Early-stage disease presents as painless self-resolving subcutaneous nodules on limbs and trunk. Methods We present the case of a young woman who presented with progressively developing, widespread painful cutaneous lesions, pyrexia of unknown origin and general malaise for one month. She had a history of hurthle cell neoplasm and a strong family history of malignancy. Initial examination revealed 1-2 cm firm, skin-coloured subcutaneous nodules over her lower back, chest and thigh, with groin and axillary lymphadenopathy. Further lesions progressively developed over a three-month period, with lesions turning increasingly erythematous and with associated ulceration. Of note, a significant periorbital lesion appeared, associated with an ipsilateral facial palsy. Results Initial bloods revealed an elevated LDH with cholestatic liver function tests. PET-CT imaging showed an enlarged axillary node with extensive pathology throughout the subcutaneous fat of unknown aetiology. Due to the family history, underlying haematological malignancy and atypical Sweet’s were considered for this unusual presentation. Seropositivity for anti-Ro and ENA, alongside raised angiotensin converting enzyme, broadened the differentials to include LEP, mixed atypical connective tissue disease and cutaneous sarcoid. Notably, complement, myositis panel and creatine kinase were normal. Lupus vulgaris was considered due to high local prevalence and excluded with T-SPOT testing. Histopathological analysis of lesional skin from the upper arm found predominantly subcutaneous infiltrates of atypical lymphoid cells with irregular hyperchromatic nuclei and rimming of individual fat cells. T-cell clonality analysis detected clonal T-cell receptor beta (V-J and D-J) gene rearrangements consistent with SPTCL. Her orbital and cutaneous lesions responded well to six cycles of CHOEP (cyclophosphamide, hydroxydaunorubicin, oncovin, etoposide, prednisone) and the patient returned to functional baseline. Conclusion This case demonstrates the diagnostic difficulties when managing a patient with relapsing remitting panniculitis. Whilst the initial presentation of SPTCL here was classical, with widespread multifocal subcutaneous nodules, the appearance of facial symptoms in SPTCL is rare. Diagnostic uncertainty is frequent in both LEP and SPTCL due to the initial non-specific cutaneous presentation. This case emphasises the importance of clinicopathological correlation for accurate diagnosis. Interestingly, up to 20% of SPTCL patients have concomitant autoimmune diseases, and there is evidence suggesting a potential association between LEP and subcutaneous SPTCL beyond chance, leading some researchers to propose that these two entities exist along a spectrum. Disclosure D. Li: None. L. Spencer: None.

Survival and Success of Dental Implants in Patients with Autoimmune Diseases: a Systematic Review.

The purpose of this systematic review is to disclose the impact of autoimmune diseases and their medical treatment on dental implant survival and success. A literature search was conducted using MEDLINE (PubMed), The Cochrane Library and Embase up to December 6th, 2021. Any clinical study on patients with an autoimmune disease in whom implant therapy was performed was eligible. The quality of included studies was assessed using the Newcastle-Ottawa Scale. For each autoimmune disease group, data synthesis was divided into three groups: 1) overall results of the autoimmune disease, 2) overall results of corresponding control groups and 3) overall results of the autoimmune disease with a concomitant autoimmune disease (a subgroup of group 1). Descriptive statistics were used. Of 4,865 identified articles, 67 could be included and mainly comprising case reports and retrospective studies with an overall low quality. Implant survival rate was 50 to 100% on patient and implant level after a weighted mean follow-up of 17.7 to 68.1 months. Implant success was sporadically reported. Data on immunosuppressive medication were too heterogeneously reported to allow detailed analysis. Overall, a high implant survival rate was reported in patients with autoimmune diseases. However, the identified studies were characterized by a low quality. No conclusions could be made regarding implant success and the effect of immunosuppressants due to heterogeneous reporting.

Pathogenetic aspects of the autoreactive form of spontaneous urticaria in adult patients

Objective: to study the parameters of the immune status and the spectrum of autoimmune markers of patients suffering from an autoreactive form of chronic spontaneous urticaria. Materials and methods: the study involved 67 patients with an autoreactive form of chronic spontaneous urticaria, with clinical and laboratory signs of autoimmune pathology, aged 18 to 65 years, who were observed on an outpatient or inpatient basis in the period from 2019 to 2022. Healthy donors without signs of chronic spontaneous urticaria (n=35) were considered as a control group. The results were evaluated according to the dynamics of clinical and functional, immunological examination. Results: when assessing the immune status of patients with autoreactive chronic spontaneous urticaria, a violation of the differentiation processes of immune-competent cells was revealed, with a predominance of T-lymphocytes with helper-inductive activity, entailing an inversion of the immune-regulatory index, activation of the humoral link of the immune system was noted: an increase in B-lymphocytes, immunoglobulins of classes A, M, G, increase of circulating immune complexes. The indicators of total IgE did not differ fundamentally from the level of donors. Changes in the parameters of the monocyte-macrophage link in patients with autoreactive form of chronic spontaneous urticaria indicated an increase in the functional activity of phagocytic cells and depletion of their reserves. Conclusion: in the autoimmune genesis of chronic spontaneous urticaria, there are significant changes in the autoimmune markers corresponding to the concomitant autoimmune disease (rheumatoid factor, antibodies (Ab) to nDNA, Ab to cardiolipin, Ab to β2-glycoprotein, Ab to neutrophils), there is a high percentage of correlation with a positive test result with autologous serum, there are features of immune status of patients with autoreactive form of chronic spontaneous urticaria.

Diagnosis and Treatment of Chronic Urticaria: The Importance of Autoimmune Aspects and Comorbidity

The study aimed to conduct a comprehensive systematic review of the literature on the autoimmune mechanisms associated with chronic spontaneous urticaria (CSU) in adults, explore the association between chronic urticaria (CU) and autoimmune disorders, analyze two case reports, and develop a diagnostic algorithm considering the autoimmune pathogenesis.
 Materials and Methods. The literature review was conducted to study the mechanisms underlying autoimmune CU. Two case reports were analyzed and a diagnostic algorithm for patients suspected of autoimmune urticaria was formulated.
 Results. CU significantly impairs patients’ quality of life, posing problems in daily activities and is often associated with concomitant autoimmune diseases. Though the pathogenesis of CSU remains incompletely understood, in recent years, there has been significant progress in understanding the pathophysiology of this condition, prompting researchers to explore new agents, especially biological ones, in cases with severe refractory urticaria. We have developed a diagnostic algorithm aimed at improving the management tactics for CSU and autoimmune pathology, that involves a thorough collection of complaints, medical history, performing a series of basic laboratory tests for specific markers of autoimmune disorders, and expanding their spectrum with detailed differential diagnostics.
 Conclusions. CU is an important medical and social issue that requires an interdisciplinary personalized approach to patients. The diagnosis of the condition involves a comprehensive approach, considering potential concomitant autoimmune disorders and detailed laboratory investigations, especially in cases refractory to standard second-generation antihistamine therapy. The treatment of CU, specifically the stepwise therapy protocol based on symptom severity and response to treatment and aimed at reducing symptoms, improving patients’ quality of life, and achieving CU remission, is outlined in various national and international guidelines, and is carried out gradually, involving three lines of therapy.

Autoimmune gastritis. Features of diagnosis and clinical course in children

Introduction. Autoimmune atrophic gastritis (AAG) is an immune-mediated disease characterized by inflammation and progressive atrophy of the mucous membrane of the fundus and body of the stomach, while the antrum remains intact for the autoimmune process. The pathogenesis of AAG is determined by the development of atrophic, hyperplastic, and metaplastic changes in the mucous membrane of the stomach body, which is a predictor of the development of neuroendocrine tumors type I. However, among pediatricians and gastroenterologists, there is still no proper alertness regarding the diagnosis of AAG. Clinical examples of complex diagnosis of AAG in children using clinical laboratory, endoscopic, and pathohistological methods are presented. To make a diagnosis, attention should be paid to concomitant autoimmune diseases, characteristic endoscopic and pathomorphological signs, as well as clinical and laboratory changes. The analysis of these changes increases the likelihood of a correct diagnosis of AAG, which is an important aspect of cancer prevention.

Identification of Shared Biomarkers and Immune Infiltration Signatures between Vitiligo and Hashimoto's Thyroiditis.

Vitiligo and Hashimoto's thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers. We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR). Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity. IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.

Tip 1 Diabetes Mellitus Tanısı Alan Çocuk ve Ergenlerde Çölyak ve Otoimmün Tiroid Hastalıkları Sıklığının Belirlenmesi

Aim: Celiac disease (CD) and autoimmune thyroid disease (AITD) are more common in individuals with Type 1 diabetes mellitus (T1DM). Hypothyroidism; has been associated with increased risk of hypoglycemia, reduced growth, and untreated CD with reduced bone mineral density has been associated with skeletal problems. It was aimed to screen the frequency of children and adolescents with T1DM in terms of CD and AITD.
 Material and Method: The patients diagnosed with T1DM in July 2015-March 2022 were retrospectively analyzed. The patients' age, gender, age at diagnosis, anti-TPO, anti-TG, Islet Cytoplasmic Antibodies (ICA), Insulin Autoantibodies (IAA), Glutamic Acid Decarboxylase (GADA) antibodies and accompanying autoimmune disease were investigated.
 Results: Chronological age was 12.5±4.4 (2.5-21.3), diagnosis of T1DM age 8.5±4.3 (1.0-17.5), duration of diabetes 4.0±3, 199 patients with T1DM aged 5 (0.0-18.1) years were included. 52.3% (n=104) of the cases were female. While the frequency of CD is 23.2% (n=10), the presence of anti-TPO and anti-TG antibodies is 6.9% (n=3) in patients whose diabetes diagnosis age is less than 5 years. Both CD and the presence of thyroid autoantibodies were more common in girls (73.3%, 68%).
 Conclusion: We found that the frequency of CD and AITD in our patients with T1DM was higher than in the general population, the frequency of CD increased in patients with a younger age at diagnosis of T1DM, anti-TPO antibodies was observed with advancing age at diagnosis, and both conditions were more common in females.

Retrospective evaluation of epidemiological and clinical data of patients diagnosed with vitiligo in our outpatient clinic

Objective: It was aimed to evaluate retrospectively the epidemiological and clinical data of patients who applied to our clinic and were diagnosed with vitiligo. Epidemiological and clinical evaluation guide the progression, choice of treatment, and diagnosis of the comorbidities of the disease. Methods: 327 patients evaluated as non-segmental vitiligo were included in the study. Demographic characteristics of the patients (age and gender), age at onset of vitiligo, treatments used for vitiligo, clinical type of vitiligo, location of lesions, and accompanying autoimmune thyroid disease data were evaluated. Results: Of 327 patients, 169 (51.7%) were male and 158 (48.3%) were female. The male/female ratio was found to be 1,1:1. The mean age of the patients was 37.26±18.07 years, and the mean age according to gender was 37.44±18.19 years in females and 37.08±18 years in males. The mean age of onset of the disease was 29.17±15.79 years, and the mean age of onset by gender was 29.13±16.46 years in females and 29.2±15.15 years in males. Regarding onset of the disease, 54% of the patients were <30 years old, and 46% of the patients were 30 years or older. Generalized vitiligo (58.8%) and acrofacial vitiligo (29.9%) were the most common clinical types. Head and neck (68.9%) and extremities (64%) were the most common locations of the lesions. Concomitant autoimmune thyroid disease was seen in 13.5% of the patients. Accompanying autoimmune thyroid disease according to gender was 19.5% in females and 7.4% in males, and there was a statistically significant difference between the groups. It was observed that 89.5% of the patients received treatment for vitiligo, and 10.5% did not receive any treatment. The most commonly used treatments were found to be topical treatment (76.1%) and topical treatment+phototherapy (14.6%). Conclusion: The epidemiological and clinical characteristics of the patients in our study were similar to other studies in the literature. Concerning the highest prevalence of generalized vitiligo in our study, phototherapy and/or systemic therapy use should have been considered when their use was indicated, and factors precluding their more widespread use could be investigated in other studies.

Autoimmune disorders associated with type 1 diabetes: clinical overview and principles of management

Type 1 diabetes mellitus is an autoimmune disease in which patients with a genetic predisposition develop antibodies against pancreatic islet β-cells under certain conditions, resulting in the loss of insulin production. Genetic, infective, dietary, and humoral factors are potential predictors associated with the risk of β-cell destruction. The coexistence of another autoimmune disease can be found in up to 29% of patients with type 1 diabetes. The most common disorders are autoimmune thyroid disease, coeliac disease, autoimmune gastritis, pernicious anaemia, and vitiligo. Other conditions that can coexist with type 1 diabetes are rheumatoid arthritis, autoimmune hepatitis, alopecia, and psoriasis. This coexistence is often present in autoimmune polyendocrine syndromes. The likelihood of developing an autoimmune disease increases with age, and it is higher in the female population. Concomitant autoimmune diseases can negatively affect the patient’s quality of life and metabolic control of diabetes, potentially increasing the risk of micro- or macrovascular complications and the frequency of hypoglycaemic episodes. Determining organ-specific antibodies is useful in the active search for autoimmune diseases in type 1 diabetes patients to identify individuals at increased risk for the disease. This article aims to summarise the most recent research on type 1 diabetes-associated autoimmune disorders, including screening, diagnosis, and treatment principles.

Predictive value of the systemic immune inflammation index and systemic inflammatory response index on omalizumab drug survival in chronic spontaneous urticaria

Abstract Background Omalizumab is recommended as adjunctive therapy for antihistamine-refractory chronic spontaneous urticaria (CSU). However, its long-term effectiveness is understudied. The systemic immune-inflammation index (SII) and the systemic inflammatory response index (SIRI) have shown prognostic value in cancer, strokes, and other diseases. Objectives This study aimed to evaluate the long-term effectiveness of omalizumab in CSU patients while investigating potential associations of SII and SIRI with the drug survival of omalizumab. Methods A retrospective study was conducted using patient data from the electronic hospital database, including patients with CSU treated with omalizumab between January 2018 and May 2021. Drug survival curves were visualized using Kaplan-Meier survival analysis. and Cox regression was utilized to assess potential associations. Results A total of 109 CSU treated with omalizumab at the University Hospital of Zurich were included. The mean drug survival was 13.6 ± 10.9 months. The mean SII and SIRI were 796.1 ± 961.3 and 2.1 ± 3.1, respectively. The multivariate model revealed that SIRI (p = 0.098) was a more robust predictor of omalizumab’s drug survival than SII (p = 0.367), while concurrent autoimmune disease or baseline immunoglobulin E (IgE) levels showed no significant impact. Conclusion This study suggests the potential utility of SIRI as a superior predictive indicator for omalizumab’s drug survival in CSU patients compared to SII. Concomitant autoimmune disease or baseline IgE levels did not significantly affect the drug’s effectiveness.

Association Vs Causation: Epidemiologic Clues As to the Autoimmune Pathogenesis of MDS

Multiple clinical associations of MDS and autoimmunity have been described, but the pathogenesis and cause-effect relationship are likely diverse and possibly intertwining. Telomeropathies, while increasing risk of bone marrow failure, can be also associated with liver or lung fibrosis and therapies for Wegener's granulomatosis can predispose to MDS. Moreover, clonal hematopoiesis (CH) seems to be more prevalent in some autoimmune diseases 1 (AD) perpetuating a process that may ultimately lead to increased risk of MDS. Reverse scenarios are also possible and AD can be a result of MDS as a form of paraneoplastic syndrome. The recently established relationship of somatic UBA1 mutations and MDS with autoimmune manifestations exemplifies such a scenario e.g., VEXAS syndrome 2. This remarkable configuration prompted us to systematically investigate the relationships between autoimmune symptomatology and MDS including genomic features such as UBA1 mutations, pathomorphological phenotypes, and demographics. We have investigated 1,903 MDS patients for the presence and the anamnestic evidence of AD. A total of 197 patients (about 10%) had a concurrent well-defined AD (5.3%) or positive inflammatory/autoimmune markers (4.9%; fibromyalgia and chronic fatigue syndrome invoked 0.3% of MDS cases and were not counted). Of those, polymyalgia rheumatica, systemic lupus erythematosus and rheumatoid arthritis were most common accounting for 13%, 5.5% and 19% of MDS cases with autoimmunity. The remaining 60% involved the presence of serological markers such as ANA, anti-RNP and anti-SSA among others (45%, 4%, 2%, respectively) without fulfilling the criteria for specific autoimmune entities. The gender distribution of cases with MDS/autoimmune features was similar to the general MDS demographics and cases without autoimmune conditions. A similar distribution was seen among males and females in both groups, with males representing 84% of each subgroup and females accounting for 16%. When stratified by risk criteria, 58% of patients with MDS/AD were found to have low risk disease (<5% of blasts) compared to patients without AD (46%; p= .74), while intermediate to high risk (HR) categories were seen in 42% and 52% (p= .74), respectively. While trisomy 8 and complex karyotype were underrepresented in MDS with AD (15% vs 22%, 4.5% vs 10%), del(11q), del(12q) and del(20q) were more common among patients with AD (10% vs 5.8%). When we screened the genomic landscape of AD/MDS, we found more mutations in TET2 (24 vs 13%, p= .004), SF3B1 (14 vs 8%, p= .026), BCORL1 (5 vs 1.5%, p= .026), DNMT3A (13 vs 6%, p= .003), IDH1 (3 vs 0.8%, p= .01), and CEBPA (3 vs 0.8%, p= .04) compared to patients without AD ( Fig.1) With a median follow up of 19 months, female patients with AD showed better 1-year survival rate of 89% vs 65% in cases without AD, (p= .044). A similar trend was seen for transformation to AML. However, such differences were not found among males. Next, we determined the etiologic fraction of the MDS/AD clinical dyad explained by the presence of VEXAS by screening UBA1 mutation in our cohort. We found mutations in 0.5% of MDS/AD vs 0.05% of the total cohort (p=0.1). To further expand on MDS association with AD, we investigated other potential autoimmune syndromes and found 0.5% of MDS with co-associated LGL with 1/3 of them presenting with RA. Notably, in the hypocellular MDS subgroup (n=175), 9.7% had concomitant AD (p= .89). Similarly, 0.3% of evaluable patients had Sweet syndrome, of which 16% associated with autoimmune conditions. Finally, since AD appear to be frequent in MDS, we queried whether in our internal cohort of CHIP patients (n=115), their prevalence could be analogous. Indeed, AD were present in a fraction similar to that of manifest MDS (around 5%). Moreover, in all of these patients, similar to those with MDS, the autoimmune diagnosis preceded that of CHIP with the caveat that, unlike MDS, CHIP may have evolved much sooner than the original diagnosis but was not screened. Our study provides valuable insights into the intricate relationship between MDS and AD. Our findings demonstrate that MDS and autoimmunity are linked through diverse mechanisms, with potential cause-effect relationships existing in both directions. Figure 1. Frequency of mutations Graph shows frequency of mutations among patients with autoimmune diseases (AD) in MDS versus those without AD.* p<0.05, **p<0.001.

Фактори ризику виникнення запальних захворювань кишечника в дітей раннього віку

In recent decades, there has been a rapid increase in the incidence of inflammatory bowel diseases in the children's population, especially in the age group under 6 years old. Risk factors significantly affect the reactive response of the child's organism and the probability of a pathology occurrence. Purpose - to analyze risk factors for the development of inflammatory bowel diseases with very early onset in children. Materials and methods. The anamnestic data of 78 examined patients with inflammatory bowel diseases - 17 patients with inflammatory bowel diseases with a very early onset and 61 children with inflammatory bowel disease that debuted over 6 years of age - were studied in detail retrospectively. Results. The anamnestic risk factors that were significantly more often observed in patients with inflammatory bowel diseases with a very early onset compared to children with inflammatory bowel diseases with an onset after 6 years of age included: spontaneous abortion in patients' mothers anamnesis, autoimmune diseases in relatives, the presence of concomitant autoimmune diseases in patients, early introduction of artificial feeding and the presence of an infectious disease just before the onset of inflammatory bowel disease. Conclusions. Taking into account the identified risk factors of inflammatory bowel diseases with a very early onset will ensure the improvement of prevention and early diagnosis of this gastrointestinal disease in young children. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the work. The informed consent of the children’s parents was obtained for the conducting the studies. No conflict of interests was declared by the authors.

Comorbid Inducible Urticaria Is Linked to Non-Autoimmune Chronic Spontaneous Urticaria: CURE Insights

Patients with chronic spontaneous urticaria (CSU) can have comorbid inducible urticaria (CIndU). How comorbid CIndU affects patients and their CSU is largely unclear. To compare patients with CSU with and without comorbid CIndUs for differences in demographic features, clinical characteristics, and laboratory markers. We analyzed 708 patients with CSU of our Urticaria Center of Reference and Excellence enrolled in CURE, the chronic urticaria registry. CURE data collected until October 2022 were used to compare patients with and without comorbid CIndU for their demographic characteristics, disease onset, activity, impact, and control, as well as concomitant allergic and autoimmune diseases and laboratory parameters associated with autoimmune CSU. Of 708 patients with CSU, 247 (35%) had comorbid CIndU. Compared with patients with standalone CSU, patients with CSU with comorbid CIndU were significantly younger, had earlier disease onset, longer disease duration, higher impact on quality of life, and a higher rate of concomitant allergic diseases. Moreover, patients with CSU with comorbid CIndU less often had features linked to autoimmune CSU such as angioedema, concomitant autoimmune diseases, eosinopenia, low levels of total IgE, and low total IgE combined with elevated anti-thyroid peroxidase IgG. Autoimmune CSU may be less common in patients with comorbid CIndU than without, and comorbid CIndU may point to autoallergic CSU.

A Single Center Experience of 13 Episodes of Acquired Hemophilia A (2019 - 2023)

Background: Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by neutralizing autoantibodies to factor VIII (FVIII). Treatment of AHA involves immunosuppression to eliminate the autoantibody and hemostatic management involving bypassing agents (BPAs). While the use of BPAs, including activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa), is primarily derived from studies of congenital hemophilia with inhibitors, registry studies of AHA have also demonstrated the efficacy of rVIIa ( Baudo et al., Blood, 2012) and aPCC ( Borg et al., Haemophilia, 2015) ( Zanon et al., Br J Haem 2019) in this population. Given the changing treatment landscape, low incidence of AHA, and high morbidity and mortality associated with the disease, our study aims to describe a single institution's experience with treating AHA. Methods: We retrospectively reviewed the records of adult patients diagnosed with AHA at a single academic medical center between January 1, 2019, and June 30, 2023. Results: Eleven patients were treated for 13 distinct episodes of AHA, with one patient admitted for three discrete episodes of AHA with responses to therapy followed by relapses once lost to follow-up. The patients were predominantly white (63.7%, n=7) and female (63.7%, n=7), with a median age of 74 years and weight of 87 kg on admission (Table 1). One patient (9.1%) had concomitant autoimmune disease. No patients presented peripartum or with active malignancy, liver disease, or a family history of bleeding disorders. The median FVIII level on admission was 1% (IQR=1%, 3.5%), with a median anti-FVIII antibody titer of 27 BU (IQR=4.5 BU, 47 BU). Given mild bleeding presentation, Patient 2 was treated as an outpatient with immunosuppression only. All patients received aPCC as the first-line BPA. Patient 5 developed uncontrolled bleeding from an arterial line despite receiving aPCC and was transitioned to rFVIIa for two days before resuming aPCC once hemostasis was achieved. The median duration of aPCC therapy was eight days. The use of aPCC (FEIBA) instead of rFVIIa (NovoSeven) as the first-line BPA led to total estimated cost avoidance of $13.5 million (calculated using average wholesale price). No patients had thrombotic events after the diagnosis of AHA. Six episodes (46.1%) were treated with prednisone and rituximab. Six episodes (46.1%) were treated with prednisone and oral cyclophosphamide. One episode (7.7%) was treated initially with prednisone and cyclophosphamide but was eventually transitioned to rituximab following a lack of response and bleeding complications after two weeks. This patient was also subsequently treated with emicizumab for five months until FVIII activity was recovered. P neumocystis jirovic i i pneumonia prophylaxis was prescribed in eight episodes (61.5%), and antiviral prophylaxis was prescribed in one episode (7.7%). No infections were noted during the follow-up period, other than two documented cases of COVID-19, one of which required admission. The median time to achieve FVIII >50% was 5.1 weeks, with a median of 8.6 months of follow-up (Figure 1). Patient 11 relapsed twice, as described in Table 1. No other patient relapsed during the follow-up period. No patient deaths occurred during the follow-up period. Conclusions: We describe 13 episodes of AHA successfully treated at a single academic medical center between 2019 and 2023. aPCC was the first-line BPA administered in all patients, with significant cost savings relative to rFVIIa. Immunosuppression, including prednisone and either cyclophosphamide or rituximab, was used to successfully eliminate autoantibodies in all patients. One patient received emicizumab for ongoing hemostatic control until achieving improvement in FVIII activity. No significant infections, thrombotic events, or deaths were noted in this cohort.

Family aggregation and prevalence of other autoimmune diseases in SAPHO syndrome

ObjectiveSAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a heterogeneous disease that clinically manifests as chronic inflammatory osteoarticular and dermatological lesions. Few reports have described familial clustering of SAPHO syndrome cases. This research aimed to illustrate the family aggregation of SAPHO syndrome and investigate the prevalence of autoimmune disorders among SAPHO syndrome patients and first-degree relatives in a large cohort. MethodsWe retrospectively reviewed the medical records of 233 SAPHO patients diagnosed at Peking Union Medical College Hospital. Direct phone calls were made to each first-degree relatives. All relatives of the patients who reported SAPHO syndrome were asked for a detailed outpatient evaluation. ResultsA total of 233 patients and 1227 first-degree relatives were recruited. Six (2.6 %) patients had positive SAPHO family history, including four mother-daughter pairs and two sister pairs. Twenty-one (9.0 %) patients presented at least one kind of autoimmune disease, including 12 rheumatoid arthritis and 4 ulcerative colitis cases. Fifty-eight (24.9 %) SAPHO syndrome patients had 68 (5.5 %) first-degree relatives with at least one autoimmune disorder. The palmoplantar pustulosis, psoriasis vulgaris, and rheumatoid arthritis prevalence in our subjects were each higher than reference rates. ConclusionThis is the first evaluation of familial aggregation for SAPHO syndrome in a large cohort. SAPHO syndrome has a weak familial aggregation. There is a relatively high prevalence of coexisting autoimmune disease among patients with SAPHO syndrome and their first-degree relatives. These results would prompt physicians to screen SAPHO syndrome patients and their family members for concomitant autoimmune diseases. KeypointsThis study suggesting a potential genetic component in the pathogenesis of SAPHO syndrome. This study is the first to evaluate the family aggregation of SAPHO syndrome in a large cohort.

Good's syndrome: brief overview of an enigmatic immune deficiency.

Good's syndrome, an infrequent adult-onset immunodeficiency is characterized by the triad of thymoma, hypogammaglobulinemia, and increased susceptibility to recurrent infections. The clinical presentation is highly variable, with a spectrum ranging from recurrent bacterial and opportunistic infections to concomitant autoimmune diseases and, sometimes malignant pathologies. Due to heterogeneous clinical phenotypes and the lack of adequate diagnostic criteria, its recognition is often challenging, even delaying it by years. It is one of the most unusual, less studied form of the immune deficiency syndromes with a still unknown pathophysiology. It was initially considered a thymoma-associated variant of primary antibody deficiencies with a reduced or absent number of mature B cells, but it later emerged that significant defects of T cell-mediated immune functions are the underlying cause of opportunistic infections. On the basis of current evidence, Good's syndrome is evaluated as a distinct acquired form of combined immunodeficiency states and classified as a phenocopy of primary immunodeficiency diseases. Epigenetic and acquired genetic factors can play an ultimate role in its evolution.

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis

Background and aimsThere is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. MethodsOnline survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Results25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment.AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response.Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response.Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. ConclusionAmong 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response.

Clinical features of myasthenia gravis with neurological and systemic autoimmune diseases.

Multiple reports on the co-existence of autoimmune diseases and myasthenia gravis (MG) have raised considerable concern. Therefore, we reviewed autoimmune diseases in MG to explore their clinical presentations and determine whether the presence of autoimmune diseases affects the disease severity and treatment strategies for MG. We reviewed all the major immune-mediated coexisting autoimmune conditions associated with MG. PubMed, Embase and Web of Science were searched for relevant studies from their inception to January 2023. There is a higher frequency of concomitant autoimmune diseases in patients with MG than in the general population with a marked risk in women. Most autoimmune comorbidities are linked to AChR-MG; however, there are few reports of MuSK-MG. Thyroid disorders, systemic lupus erythematosus, and vitiligo are the most common system autoimmune diseases associated with MG. In addition, MG can coexist with neurological autoimmune diseases, such as neuromyelitis optica (NMO), inflammatory myopathy (IM), multiple sclerosis (MS), and autoimmune encephalitis (AE), with NMO being the most common. Autoimmune diseases appear to develop more often in early-onset MG (EOMG). MS coexists more commonly with EOMG, while IM coexists with LOMG. In addition, MG complicated by autoimmune diseases tends to have mild clinical manifestations, and the coexistence of autoimmune diseases does not influence the clinical course of MG. The clinical course of neurological autoimmune diseases is typically severe. Autoimmune diseases occur most often after MG or as a combined abnormality; therefore, timely thymectomy followed by immunotherapy could be effective. In addition, thymoma-associated AChR MG is associated with an increased risk of AE and IM, whereas NMO and MS are associated with thymic hyperplasia. The co-occurrence of MG and autoimmune diseases could be attributed to similar immunological mechanisms with different targets and common genetic factor predisposition. This review provides evidence of the association between MG and several comorbid autoimmune diseases.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment—Results From CURE

Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood. To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response. Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022). Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H1-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively). Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.