Comorbid Autoimmune Diseases Research Articles

Chemical-Associated Vitiligo

An otherwise healthy man in his 40s presented with white macules and patches that appeared on his skin several years ago. Initially, he noticed asymptomatic white discoloration on the ventral aspect of wrists, with subsequent involvement of thehead and neck. He had no relevant medical, drug, or family history, except for thyroid dysfunction in his mother. He worked in a laundry facility, with frequent exposure to detergents. Examination revealed well-demarcated hypopigmented patches without erythema or scaling on the ventral forearms (Figure 1). One patch on the occipital area scalp showed white discoloration of the associated hair (Figure 2). Wood's lamp examination showed no accentuation. Based on the patient’s history of exposure by frequently implicated chemicals, as well as the morphology and distribution of skin lesions, a diagnosis of chemical-associated vitiligo was made.Figure 2Well-defined coalescing hypopigmented patches on ventral forearm.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Chemical-associated vitiligo, an acquired disorder that presents with hypo- or depigmented patches, is thought to be induced by repeated exposure to specific chemicals.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Several chemical compounds have been implicated, most of which contain phenol groups in their chemical structure. Because the phenol group constitutes a part of the amino acid tyrosine, the precursor of melanin, it has been hypothesized that phenol-containing compounds act as tyrosine analogs when applied to the skin, thereby interfering with melanogenesis.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Others have hypothesized that depigmenting chemicals produce metabolites that are toxic to melanocytes or overwhelm the melanocyte ability to withstand oxidative stress.2Boissy R.E. Manga P. On the etiology of contact/occupational vitiligo.Pigment Cell Res. 2004; 17: 208-214Crossref PubMed Scopus (207) Google Scholar In cases of occupational exposure, as in our patient, the hands and forearms are frequently involved. However, some reports demonstrated that lesions could appear in remote areas: that is, those not in direct contact with chemical substances.3Bonamonte D. Vestita M. Romita P. Filoni A. Foti C. Angelini G. Chemical leukoderma. dermatitis: contact, atopic, occupational, drug.Dermatitis. 2016; 27: 90-99Crossref PubMed Scopus (16) Google Scholar This observation has led to invocation of the autoimmune theory, proposing that chemical-induced stress in melanocytes initiates an autoimmune response, leading to their destruction. Subsequently, this immune response can affect other melanocytes in distant regions that are not directly in contact with the chemical.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar By contrast, idiopathic vitiligo commonly affects the periorificial areas, nipples, and genitals. Chemical-associated vitiligo represents a diagnostic challenge, as it is often difficult to differentiate it from idiopathic vitiligo based on the clinical as well as the histopathological presentation.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar The presence of 3 out of the following 4 criteria are considered sufficient for establishing the diagnosis of chemical-associated vitiligo: acquired vitiligo-like depigmented lesion(s), history of repeated exposure to specific chemical compounds, patterned vitiligo-like macules at site of exposure, and confetti macules.4Ghosh S. Mukhopadhyay S. Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country.Brit J Dermatol. 2009; 160: 40-47Crossref PubMed Scopus (69) Google Scholar Thorough history taking is essential to diagnose chemical-associated vitiligo and identify the possible culprit. Presumably, chemical-associated vitiligo does not confer the same increase in associated autoimmune conditions as does idiopathic vitiligo, although this is not well studied.5Gill L. Zarbo A. Isedeh P. Jacobsen G. Lim H.W. Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: a cross-sectional study.J Am Acad Dermatol. 2016; 74: 295-302Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar In many cases, strict avoidance of the offending chemical agent allows the condition to self-resolve. Moreover, chemical-associated vitiligo tends to respond better to skin-directed treatments than idiopathic vitiligo.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar

Neuroimmune Contributions to T-Lymphocyte-Driven Inflammation in a Preclinical Model of Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder, and PTSD patients have a >3 fold risk of developing comorbid autoimmune diseases. While the etiology of this increased risk remains unclear, a known hallmark of PTSD is increased sympathetic tone. Therefore, we hypothesized that sympathoexcitation in PTSD may be causally linked to inflammation and the predisposition to autoimmunity.

Neuroimmune Contributions to T‐lymphocyte‐Driven Inflammation in a Preclinical Model of Post‐traumatic Stress Disorder (PTSD)

Post‐traumatic stress disorder (PTSD) is a devastating psychological disorder with an idiopathic etiology. Interestingly, patients with PTSD have a >3 fold risk of developing comorbid autoimmune diseases compared to matched controls, yet, the exact mechanisms underlying this risk remain unclear. A hallmark of PTSD is increased sympathetic tone, and previous work from our lab has shown that immune cells, primarily T‐lymphocytes, display an autoreactive phenotype when exposed to elevated levels of norepinephrine (NE). Therefore, we hypothesized that the sympathoexcitation observed in PTSD may be causally linked to T‐lymphocyte‐driven inflammation and the predisposition to autoimmune diseases. To test this hypothesis, we adapted a preclinical mouse model of PTSD known as social defeat stress. After validating the PTSD‐like behavioral phenotype of our trauma‐exposed mice, we investigated the neuroimmune interactions of T‐lymphocytes in the spleen that may govern the increased predilection for inflammatory diseases in PTSD patients. The spleen is a primary site of adaptive immune system activation, and is innervated exclusively by the sympathetic efferent splenic nerve. Trauma‐exposed animals exhibited a 2.5 fold increase in splenic catecholamines and 4.1 fold increase in splenic tyrosine hydroxylase (TH) content (p<0.05) compared to controls. Additionally, purified splenic T‐lymphocytes from socially‐defeated mice showed elevations in the pro‐inflammatory cytokines interleukin 6 (IL‐6, 1.84 fold increase, p<0.0001) and interleukin 17A (IL‐17A, 5.5 fold increase, p=0.0032). Importantly, TH content was tightly correlated with T‐lymphocyte IL‐6 and IL‐17A expression (R=0.43, p=0.0001 and R=0.87, p<0.0001, respectively), suggesting a neuroimmune mechanism of pro‐inflammation. To test this, we performed targeted splenic denervation to deduce the contribution of the splenic nerve to T‐lymphocyte‐driven inflammation after psychological trauma. Denervation reduced splenic NE content by 80% (p<0.0001), and persisted to at least 30 days after denervation. While splenic denervation did not alter the PTSD‐like behavioral changes after social defeat, denervation ameliorated the characteristic increase in gene expression of splenic T‐lymphocyte IL‐6 and IL‐17A after social defeat stress. Overall, our data suggest that psychological trauma results in altered inflammation through sympathetic modulation of splenic T‐lymphocytes. Further elucidation of this neuroimmune interaction will provide possible new biomarkers or therapeutic strategies to reduce the inflammatory‐driven morbidity and mortality of PTSD patients.Support or Funding InformationNIH R00HL123471, T32NS105594

Genital vitiligo in children: Factors associated with generalized, non-segmental vitiligo.

It remains uncertain as to whether genital vitiligo of childhood is segmental or a forme fruste of non-segmental disease. This type of vitiligo is sometimes termed figure-of-eight disease due to female predominance and perineal and perianal hypopigmentation or depigmentation around two orifices, the anal and vaginal introitus. The objective of this series was to categorize the features of genital-limited vitiligo of childhood including comorbidities, family history, and long-term course. IRB-approved retrospective chart review of vitiligo cases. Eight cases of vitiligo that began in childhood in the genital area were identified, including clinical course and comorbidities. Involvement of the contiguous skin, including inner thighs, buttocks, and scrotum, was noted in all males. In females, only 1 patient had other sites of vitiligo, which was a solitary lesion on the chest. Therapeutic response to topical corticosteroids for perianal skin was seen in five of six children and topical calcineurin inhibitors with or without calcipotriene in four out of four patients. Segmental disease limited to the genitalia was more common in females than males, suggesting that perhaps intervention and work-up for comorbid autoimmune diseases may be required for males with genital-limited vitiligo at onset, but may be deferred in females and added if observation of spread is noted. Differentiation from lichen sclerosus et atrophicus may require biopsy.

Chronic nonbacterial osteomyelitis in children: a multicenter case series.

Chronic nonbacterial osteomyelitis (CNO) is a primary autoinflammatory bone disease that presents more frequently in children and is characterized by inflammatory bone lesions in the absence of an infectious etiology. There is little information of this disease in Latin America. The objective of the study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of pediatric CNO patients. The clinical records of 19 patients with CNO diagnosed between 2007 and 2019 at three tertiary centers in Santiago, Chile were reviewed. The median age of onset was 10years and 47% were female. Median delay in diagnosis was 12months. All patients had a pattern of recurrent multifocal disease. 37% of patients had positive antinuclear antibodies and 16% HLA-B27 positivity. 21% of patients presented arthritis or other rheumatologic comorbidity, although no association with psoriasis, inflammatory bowel disease (IBD) or palmoplantar pustulosis (PPP) was observed. Eighteen patients received treatment with nonsteroidal anti-inflammatory drugs with partial response. Twelve patients received methotrexate, and half of them received steroids at the same time reaching remission in 50%. Of the five patients who received bisphosphonates, 60% achieved remission. All four patients who received adalimumab had comorbid arthritis and 75% achieved remission. In a series of Chilean children with CNO, all patients presented with multifocal lesions. Comorbid autoimmune diseases including arthritis were frequent, but no association was observed with psoriasis, IBD, or PPP.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study

BackgroundMyasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis.MethodsPatients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic.ResultsA total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161).ConclusionsJuvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population

Vitiligo is associated with medical conditions, primarily autoimmune disorders; however, only a few studies in the United States have investigated these associations. Our purpose was to investigate the diseases associated with vitiligo in the New York, New York, population and evaluate if these associations differ by race/ethnicity and sex. In this retrospective study, we analyzed data collected from the medical records of 1487 vitiligo patients seen at New York University during a 10-year period. Vitiligo patients had a statistically significant higher prevalence of hypothyroidism, multiple sclerosis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, seronegative arthritis, pernicious anemia, myasthenia gravis, inflammatory bowel disease, lymphoma, and systemic lupus erythematosus. Rates of comorbid autoimmune diseases varied by race and sex. Medical charts did not consistently report race/ethnicity, type of vitiligo, and total body surface area affected. Information from nondermatology medical visits was also included. This study revealed multiple new disease associations for vitiligo, including multiple sclerosis, idiopathic thrombocytopenic purpura, and lymphoma, as well as confirmed previously reported associations with other autoimmune diseases, the most common being hypothyroidism followed byrheumatoid arthritis. Associations did vary by race/ethnicity and sex.

1671-P: Comorbid Autoimmune Disease in Participants at Risk for Type 1 Diabetes

People with type 1 diabetes (T1D) are at increased risk for comorbid autoimmune disease (CAID). The TrialNet Pathway to Prevention (PTP) Study screens relatives of people with T1D for islet autoantibodies (Ab) to determine T1D risk. PTP Ab+ participants self-reported (Y vs. N) whether or not they had CAIDs at the start of monitoring. Outside of celiac disease, CAID has not been examined in Ab+ participants. Of the 5,740 Ab+ participants, 586 (10.2%; 95% CI: 9.4 - 11.0%) reported having a CAID. Of those with a single confirmed Ab+, GADA+ participants had a higher prevalence of CAID (230/1709=13.5%) vs. those who were IA-2A+ (8/88=9.1%) or mIAA+ (40/592=6.8%; p<0.0001). Across all Ab+ participants, the number of Abs was inversely associated with prevalence of CAID at baseline, where a higher number of Abs corresponded to a lower likelihood of CAID (1 Ab+: 278/2393=11.6%; 2 Ab+: 165/1388=11.9%; 3 Ab+: 73/891=8.2%; 4 Ab+: 44/687=6.4%; 5 Ab+: 26/381=6.8%; p<0.0001). The most prevalent CAID reported was thyroid disease (5.7%) with celiac disease reported in 1.3%. The influence of HLA status on CAID prevalence was mixed; celiac disease was more prevalent in those with DR3 (OR=2.79, p<0.0001) while thyroid disease was less prevalent in those with DR4/DQ8 (OR=0.61, p<0.0001). Although being single confirmed Ab+ at screening was associated with a higher likelihood of having CAID in the univariate setting, it was significantly protective (OR=0.77; p=0.007) when adjusting for age, sex and HLA status. In multivariable logistic regression models, the prevalence of CAID at baseline was associated with older age, being female and HLA DR4/DQ8 negative. In conclusion, the reported prevalence rates of CAID is high in Ab+ relatives of people with T1D, inversely correlated with the number of Ab present, and related to DR3 and DR4/DQ8 haplotypes. The change in the direction of association of CAID with Ab number after an adjustment for HLA status suggests that DR3 and DR4/DQ8 could contribute to both CAID and Ab development. Disclosure K. Simmons: None. S. Geyer: None. D.K. Wherrett: None. H.M. Ismail: None. M. Lundgren: None. L.E. Bocchino: None. J.M. Sosenko: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. A. Steck: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK0855095, K12DK094712-08)

Immune-mediated comorbidities in Saudi patients with narcolepsy.

Background: Autoimmunity has been proposed as a cause of narcolepsy. A few studies have assessed comorbid autoimmune diseases in patients with narcolepsy, with conflicting results; however, no study has assessed autoimmune diseases in Arab narcolepsy patients. This study aimed to assess the coexistence of immune-mediated conditions such as allergies, autoimmune diseases, and autoinflammatory diseases in patients with narcolepsy type 1 (with cataplexy) (NT1) and narcolepsy type 2 (without cataplexy) (NT2).Methods: Personal and family history of autoimmune/autoinflammatory and allergic disorders was collected using a questionnaire in 80 consecutive Saudi patients with narcolepsy (46 NT1 and 24 NT2), who were diagnosed according to the International Classification of Sleep Disorders, Third Edition. The control group comprised 222 adults from the general population.Results: Comorbid autoimmune/autoinflammatory diseases were reported by 21.4% of the NT1 patients, and 12.2% of the controls, with no significant difference between cases and controls in a model adjusted for confounding covariates. However, allergic disorders were significantly more prevalent among NT1 patients. Both comorbid autoimmune/autoinflammatory and allergic disorders were significantly more prevalent among NT2 patients compared to controls. No differences in demographic and clinical characteristics were detected between narcolepsy patients with and without autoimmune/autoinflammatory diseases.Conclusion: NT1 is not associated with increased comorbid autoimmune diseases in the studied sample of Saudi patients. However, autoimmune diseases are associated with NT2, and allergic disorders are associated with both NT1 and NT2. These findings suggest the existence of dysregulation in the immune system of narcolepsy patients that requires further research.

Immunogenicity of pneumococcal vaccines in comorbid autoimmune and chronic respiratory diseases

ABSTRACT Streptococcus pneumoniae causes pneumonia, meningitis, otitis media, and bacteremia. The mortality and morbidity of invasive pneumococcal disease are high among adults aged >65 years or those with underlying chronic or immunosuppressive conditions. A recent systematic review showed that patients treated with immunosuppressive agents have impaired immune responses to pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine compared with healthy subjects. A more favorable response is observed in patients treated with tumor necrosis factor-alpha-blocking agents compared with those treated with other immunosuppressive agents. Low systemic corticosteroid doses do not affect the responses to pneumococcal vaccines. Patients with human immunodeficiency virus and idiopathic pulmonary fibrosis receiving immunosuppressive therapy exhibit decreased immunogenicity to pneumococcal vaccines. The effects of T-cell-dependent PCV possibly depend on host memory B cells in some disease conditions. Several immunosuppressive therapy types and disease conditions may affect the responses to pneumococcal vaccines. Immunization should be administered before immunosuppressive medication initiation whenever possible.

Disease Presentation and Remission Rate in Graves Disease Treated With Antithyroid Drugs: is Gender Really A Factor?

Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs. Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015. Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively ( P = .55). Remission rates were 47% in men and 58% in women ( P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy. Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders. ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

35-Year-Old Man With Episodic Fever and Cough

35-Year-Old Man With Episodic Fever and Cough

High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database.

Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.

Comorbid autoimmune diseases and cancer risks among patients with alopecia areata: A population-based case-control study in Korea

Comorbid autoimmune diseases and cancer risks among patients with alopecia areata: A population-based case-control study in Korea

Autoimmune disease, familial clustering and thyroid carcinoma coexistent with autoimmune thyroiditis in children and adolescence: A cross-sectional study from the Czech Republic.

The prevalence of autoimmune thyroiditis (AIT), as the most common autoimmune disease (AD) and papillary thyroid cancer (PTC) is steadily rising in children. The aim of this study was to determine the coexistence of other AD and thyroid carcinoma (TC) in AIT. The cross-sectional study conducted at a tertiary center comprised AIT children (< 19 years). Data on age/sex, thyroid function and ultrasound, autoantibodies, associated AD, familial occurence of AD and the occurence of TC for each child were collected. In total, 231 eligible patients (77% females) were included. The most common onset (66%) was during adolescence. At onset, hypothyroidism was detected in 59.3%; hashitoxicosis in 1.3%. The positivity of both autoantibodies was present in 60.6%, the negativity was in 3,5%. We confirmed a high frequency (44.6%) of AD with AIT predominance in parents and/or grandparents of patients and in siblings (7.4%). 15.2% had at least 1 comorbid AD, of which type 1 diabetes mellitus was the most common (8.5%). Over a period of 7 years TC was diagnosed in 16 patients (mean age 13.5 years) with predominance of PTC in 15 (94%) patients. AIT had concurrently 69% patients. 56% of patients had metastases (89% in AIT subjects). An invasive PTC was present in 44% (86% in AIT subjects). The prevalence rate of AD in AIT and first-degree relatives is high, and several new associations have been reported. Providers should be aware of comorbidities and TC in AIT as this would help in early diagnoses and timely interventions.

Comorbidities in vitiligo: comprehensive review.

Vitiligo is a common skin disorder characterized by idiopathic, progressive cutaneous hypomelanosis. Vitiligo is associated with several comorbid autoimmune, systemic, and dermatological diseases, primarily thyroid disease, alopecia areata, diabetes mellitus, pernicious anemia, systemic lupus erythematosus, rheumatoid arthritis, Addison's disease, inflammatory bowel disease, Sjögren's syndrome, dermatomyositis, scleroderma, ocular and audiological abnormalities, psoriasis, and atopic dermatitis. It is essential to increase awareness of these comorbidities in order to improve the disease burden and quality of life of patients with vitiligo. Herein, we review the association with the most frequent comorbidities associated with vitiligo.

Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults.

Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

Autoimmunity in postural orthostatic tachycardia syndrome: Current understanding.

There is growing interest in the role of autoimmunity in postural orthostatic tachycardia syndrome (POTS). In recent years, investigators have described an increased rate of co-morbid autoimmune disease, and the presence of several neural receptor autoantibodies and non-specific autoimmune markers in POTS. Case reports on the efficacy of immunotherapy in highly selected POTS patients continue to appear in the literature, while no prospective clinical trials have occurred to date. This article summarizes the current state of knowledge on the role of autoimmunity in POTS, the clinical implications of these findings, and prospects for future research.

Age-adjusted Charlson comorbidity score is associated with the risk of empyema in patients with COPD.

Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of pneumonia than the general population due to their impaired lung defense. They also have a higher risk of empyema and more comorbidities than patients without COPD. This study aimed to evaluate the risk of empyema in patients with COPD after adjusting for age and comorbidities using the age-adjusted Charlson comorbidity index (ACCI).Data were retrieved from the National Health Insurance Research Database. COPD patients were defined as inpatients aged >40 years with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for COPD. In total, 558,660 COPD patients were enrolled and separated into 3 groups by ACCI score to represent the severity of comorbidity (≤2, 3–5, and >5). Other comorbidities assessed included autoimmune diseases, gastroesophageal reflux disease, dyslipidemia, chest wall injury, and thoracostomy.Of the 558,660 patients, 36,556 (6.54%) had low ACCI scores (≤2), 208,292 (37.28%) had moderate ACCI scores (3–5), and 313,812 (56.17%) had high ACCI scores (>5). The mean ages of the low, moderate, and high groups were 50.66, 70.62, and 78.05 years, respectively. The hazard ratio (HRs) for empyema were 1.26 (95% confidence interval (CI) = 1.13–1.40) in the moderate ACCI group and 1.55 (95% CI = 1.39–1.72) in the high ACCI group compared with the low ACCI group. The overall incidence of empyema in COPD patients was 2.57 per 1000 person-years.This is the first study to use ACCI scores to analyze the risk of empyema in patients with COPD. Patients with high ACCI scores were older and had more complicated comorbidities, resulting in a higher risk of empyema and poor prognosis. The subgroup analysis indicated that COPD patients with comorbid autoimmune disease, gastroesophageal reflux disease, chest wall injury, or history of thoracostomy did not have a higher risk of empyema than patients without these comorbidities.Empyema is an important issue in patients with COPD and is associated with significant morbidity and mortality. Awareness of the risk factors for empyema, close monitoring, and early intervention may improve patient outcomes and decrease mortality.

Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan.

Previous studies have proposed the association between pemphigus and several autoimmune diseases, but no large-scale study has been reported. To delineate the association between pemphigus and autoimmune diseases including psoriasis. A total of 1,998 patients with pemphigus and 7,992 control subjects were enrolled from the National Health Insurance Research Database in Taiwan from 1997 to 2010. The odds of comorbidities between these two groups were analysed by multivariate logistic regression. Compared with control subjects, patients with pemphigus were much more likely to have Sjögren's syndrome (odds ratio [OR]: 15.0; 95% confidence interval [CI]: 3.16-71.5), psoriasis (OR: 7.18; 95%CI: 5.55-9.29), systemic lupus erythematosus (OR: 4.46; 95%CI: 1.88-10.6), and alopecia areata (OR: 2.68; 95%CI: 1.26-5.67). According to gender-stratified analyses, however, the association between pemphigus and Sjögren's syndrome or alopecia areata was found to be significant only in the female patients. We confirm the association between pemphigus and some autoimmune diseases, including Sjögren's syndrome, systemic lupus erythematosus, and alopecia areata. In addition, we present the novel finding that patients with pemphigus have an increased risk of psoriasis.