Publications by authors named "Arnon D Cohen"

202 Publications

Risk of COVID-19 and its complications in patients with atopic dermatitis undergoing dupilumab treatment-a population-based cohort study.

Immunol Res 2021 Oct 13. Epub 2021 Oct 13.

Clalit Health Services, Tel-Aviv, Israel.

The risk of coronavirus disease (COVID-19) infection and its complications among patients with atopic dermatitis (AD) treated by dupilumab is yet to be determined. We aimed to assess the risk of SARS-CoV-2 infection, COVID-19-associated hospitalization, and mortality among patients with AD treated by dupilumab. A population-based cohort study was conducted to compare AD patients treated by dupilumab (n = 238) with those treated by prolonged systemic corticosteroids (≥ 3 months; n = 1,023), phototherapy (n = 461), and azathioprine or mycophenolate mofetil (MMF; n = 194) regarding the incidence of COVID-19 and its complications. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality among patients treated by dupilumab was 70.1 (95% CI, 40.5-116.4), 5.0 (95% CI, 0.3-24.7), and 0.0 per 1,000 person-year, respectively. The use of dupilumab was not associated with an increased risk of SARS-CoV-2 infection [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 1.13 (95% CI, 0.61-2.09); dupilumab vs. phototherapy: 0.80 (95% CI, 0.42-1.53); dupilumab vs. azathioprine/MMF: 1.10 (95% CI, 0.45-2.65)]. Dupilumab was associated with a comparable risk of COVID-19-associated hospitalization [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 0.35 (95% CI, 0.05-2.71); dupilumab vs. phototherapy: 0.43 (95% CI, 0.05-3.98); dupilumab vs. azathioprine/MMF: 0.25 (95% CI, 0.02-2.74)]. When applicable, the risk of mortality was not elevated in patients with AD treated by dupilumab [HR for dupilumab vs. prolonged systemic corticosteroids: 0.04 (95% CI, 0.00-225.20)]. To conclude, dupilumab does not impose an increased risk of SARS-CoV-2 infection or COVID-19 complications in patients with AD. Dupilumab should be continued and considered as a safe drug for moderate-to-severe AD during the pandemic.
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http://dx.doi.org/10.1007/s12026-021-09234-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514206PMC
October 2021

The Association of Bullous Pemphigoid With Atopic Dermatitis and Allergic Rhinitis-A Population-Based Study.

Dermatitis 2021 Sep 27. Epub 2021 Sep 27.

From the Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany Azrieli Faculty of Medicine, Bar-Ilan University, Safed Unit of Dermatology, Baruch Padeh Poria Medical Center, Tiberias Clalit Health Services, Tel-Aviv Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences Otolaryngology Department, Barzilai University Medical Center, Ben-Gurion University of the Negev, Beer Sheva Department of Behavioral Sciences, Ariel University Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Background: Although bullous pemphigoid (BP), atopic dermatitis (AD), and allergic rhinitis (AR) are associated with shared pathogenic mechanisms the epidemiological relationship between these conditions remains to be investigated.

Objective: To evaluate the bidirectional association of BP with AD and AR.

Methods: A population-based retrospective cohort study was performed comparing BP patients (n = 3924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280), with respect to incident cases of AD and AR. A case-control design was additionally adopted to assess the odds of BP in individuals with a preexisting diagnosis of AD and AR.

Results: The odds of BP was increased after a preexisting diagnosis of AD (fully adjusted odds ratio, 1.76; 95% confidence interval [CI], 1.44-2.15; P < 0.001) and AR (fully adjusted odds ratio, 1.13; 95% CI, 1.01-1.28; P = 0.047). Patients with BP were at an increased risk of subsequent AD (fully adjusted hazard ratio, 2.00; 95% CI, 1.60-2.51; P < 0.001) but not AR (fully adjusted hazard ratio, 1.00; 95% CI, 0.83-1.20; P = 0.997). Compared with other patients with BP, those with BP and comorbid AD and AR were more frequently managed by adjuvant drugs and long-term systemic and topical corticosteroids and had decreased all-cause mortality.

Conclusions: A history of AD and AR confers susceptibility to the development of BP. Awareness of this association may be of help for physicians managing patients with these diseases.
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http://dx.doi.org/10.1097/DER.0000000000000792DOI Listing
September 2021

Reply to letter.

Arthritis Care Res (Hoboken) 2021 Aug 26. Epub 2021 Aug 26.

Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.

We thank Li et al for their commentary on our recently published paper "Mortality in Ankylosing Spondylitis According to Treatment: A Nationwide Retrospective Cohort Study of 5900 Patients from Israel" (1). Their major concern was regarding the findings which demonstrated no excess mortality in ankylosing-spondylitis (AS) patients treated with TNF-inhibitors (TNFi).
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http://dx.doi.org/10.1002/acr.24771DOI Listing
August 2021

Hidradenitis suppurativa and rheumatoid arthritis: evaluating the bidirectional association.

Immunol Res 2021 Aug 19. Epub 2021 Aug 19.

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.

Despite some common pathogenic themes, the association of hidradenitis suppurativa (HS) and rheumatoid arthritis (RA) has been poorly investigated. We aimed to evaluate the bidirectional association between HS and RA. A population-based study was conducted to compare HS patients (n = 6779) with age-, sex- and ethnicity-matched control subjects (n = 33,260) with regard to the incidence of new-onset and the prevalence of preexisting RA. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated. The prevalence of preexisting RA was greater among patients with HS relative to controls (0.5% vs 0.3%. respectively; p = 0.019). The odds of being diagnosed with HS were 1.6-fold higher in patients with a history of RA (fully-adjusted OR, 1.66; 95% CI, 1.11-2.49; p = 0.014). The incidence rate of new-onset RA was estimated at 4.3 (95% CI, 2.5-6.8) and 2.4 (95% CI, 1.8-3.2) cases per 10,000 person-years among patients with HS and controls, respectively. The risk of RA was comparable between patients with HS and controls (fully-adjusted HR, 1.45; 95% CI, 0.77-2.72; p = 0.249). Compared to other patients with HS, those with HS and comorbid RA were older, had a higher prevalence of diabetes mellitus, hypertension, and hyperlipidemia, and had a comparable risk of all-cause mortality. In conclusions, a preexisting diagnosis of RA predisposes individuals to develop HS. Clinicians managing patients with HS and RA should be aware of this association. Further research is required to delineate the underlying pathomechanism of this observation.
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http://dx.doi.org/10.1007/s12026-021-09221-4DOI Listing
August 2021

Biosimilars for the treatment of patients with psoriasis: A consensus statement from the Biosimilar Working Group of the International Psoriasis Council.

JAAD Int 2020 Dec 23;1(2):224-230. Epub 2020 Nov 23.

Department of Dermatology, Manchester Academic Health Science Center, Salford Royal Hospital (Hope), The University of Manchester, Salford, United Kingdom.

Background: As biosimilars have become available in various parts of the world, the International Psoriasis Council has reviewed aspects of their use.

Objective: To provide consensus statements from the Biosimilar Working Group about the use of biosimilars in patients with psoriasis.

Methods: A semiqualitative structured process was employed to approve the consensus statements on biosimilars using the nominal group technique. The final statements were validated by a survey of the paricipants. The approval of the consensus statements was predefined as >80% positive opinions.

Results: A consensus was reached in 36/38 statements regarding regulatory considerations, extrapolation of indication, interchangeability, substitution at the pharmacy level, pharmacovigilance, traceability, naming, biosimilar policy, education, and cost of biosimilars. Example statements include "Switching a stable patient from a reference product to a biosimilar product is appropriate if the patient and physician agree to do so" and "Patients and patients' organisations should be involved in all decision making and policy development about the use of biosimilars."

Conclusion: The International Psoriasis Council Biosimilar Working Group provides consensus statements for the use of biosimilars in the treatment of patients with psoriasis. We suggest that these statements provide global guidance to clinicians, healthcare organizations, pharmaceutical companies, regulators, and patients regarding the development and use of biosimilars in patients with psoriasis.
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http://dx.doi.org/10.1016/j.jdin.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361899PMC
December 2020

[ETIOLOGIES OF EXTREME HYPERFERRITINEMIA - ANALYSIS OF A LARGE DATABASE].

Harefuah 2021 Aug;160(8):527-532

Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Israel.

Introduction: Besides its role in iron homeostasis and storage, ferritin is also regarded as an acute-phase reactant. Extreme Hyperferritinemia is seen in severe inflammatory conditions, severe infections, iron storage diseases and malignancies. A direct linkage between high ferritin levels and poor prognosis has been observed.

Objectives: To characterize patients with extreme high ferritin levels in the serum for possible etiologies and assessment of the correlation between ferritin levels, prognosis and mortality.

Methods: We conducted a retrospective cohort study between the years 2002-2016 using the large database of Clalit Health Services. Patients older than 18 years with ferritin levels above 10,000 ng/ml that were taken during hospitalization and ambulatory visits were included in the study. After examining the medical files of each patient, we evaluated the demographic characteristics, etiologies, clinical presentation and relevant laboratory parameters. We calculated the proportion of this data and compared it to the general population by using chi square test.

Results: The incidence of extreme hyperferritinemia was statistically significant in patients with autoimmune and rheumatologic diseases in particular adult onset Still's disease compared to the general population. Among hospitalized patients, bacterial and viral infections were the leading cause in 62% of cases. In ambulatory patients, hyperferritinemia was mainly secondary to chronic blood transfusions in patients with hemoglobinopathies and poor compliance to iron chelators. Among 21 biopsies from involved organs including lymph nodes, bone marrow and liver, hemophagocytosis was only observed in 5 cases (6.8%).

Conclusions: Extreme hyperferritinemia with values higher than 10,000 ng/ml can be attributed to many inflammatory autoimmune conditions.
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August 2021

Utilisation of healthcare services and drug consumption in fibromyalgia: A cross-sectional analysis of the Clalit Health Service database.

Int J Clin Pract 2021 Nov 18;75(11):e14729. Epub 2021 Aug 18.

Department of Medicine 'B', Sheba Medical Center, Tel-Hashomer, Israel.

Aim: To investigate the health care utilisation and drug consumption of patients with fibromyalgia (FM).

Materials And Methods: This is a cross-sectional study using the Clalit Health Care database. Clalit is the largest HMO in Israel, serving more than 4.4 million enrollees. We identified FM patients and age and sex-matched controls. Indicators of healthcare utilisation and drug consumption were extracted and analysed for both groups.

Results: The study included 14 296 FM patients and 71 324 controls. The mean age was 56 years, with a women predominance of 92%. The mean number of visits across of all healthcare services (hospitalisations, emergency department visit, general practitioner clinic visits, rheumatology clinic visits, and pain clinic visits) and the mean difference (MD) were significantly higher for FM patients compared with controls (MD 0.66, P < .001; MD 0.23, P < .001; MD 7.49, P < .001; MD 0.31, P < .001; MD 0.13, P < .001), respectively. Drug use was significantly and consistently higher among FM patients compared with controls; NSAIDs (non-steroidal anti-inflammatory drugs) OR 2.56, P < .001; Opioids OR 4.23, P < .001; TCA (tricyclic antidepressants) OR 8.21, P < .001; Gabapentinoids OR 6.31, P < .001; SSRI (selective serotonin reuptake inhibitors) OR 2.07, P < .001; SNRI (serotonin-norepinephrine reuptake inhibitor) OR 7.43, P < .001.

Conclusion: Healthcare utilisation and drug use are substantially higher among patients with FM compared with controls.
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http://dx.doi.org/10.1111/ijcp.14729DOI Listing
November 2021

The risk of depression and anxiety in patients with familial mediterranean fever - a cross-sectional study.

J Affect Disord 2021 09 6;292:695-699. Epub 2021 Jun 6.

Division of Psychiatry, Barzilai Medical Center, Ashkelon, Israel.

Background: Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease associated with various systemic comorbidities. Recent research regarding the association with depression and anxiety has yielded conflicting results. The current study aims were to examine whether such an association exists using big data analysis methodology.

Methods: This study was conducted as a cross-sectional analysis based on the Clalit Health Services database. We compared the proportions of depression and anxiety in patients diagnosed with FMF and age- and sex- matched controls. We used the Chi-square test and T-test for univariate analysis. Multivariate logistic regression was then applied to control for possible confounding variables.

Results: The study included 7,670 patients with FMF and 7,670 matched controls. The prevalence of both depression and anxiety was found to be higher in the FMF group as compared to controls (6.22% and 4.58%, respectively, p<0.001, and 4.93% and 3.14%, respectively, p<0.001). These proportions remained significant after adjusting for important confounders, such as smoking and socioeconomic status.

Limitations: Temporal association does not indicate a causal relationship, the validity of the diagnoses relies on clinical records and is not based on formal classifications or diagnostic criteria, information regarding disease duration and other parameters were not accessible.

Conclusions: Our data imply that FMF is independently associated with both depression and anxiety. These findings highlight the importance of raising awareness for these comorbidities.
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http://dx.doi.org/10.1016/j.jad.2021.05.113DOI Listing
September 2021

The Burden of Coronavirus Disease 2019 and Its Complications in Patients With Atopic Dermatitis-A Nested Case-Control Study.

Dermatitis 2021 Oct;32(1S):S45-S52

Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

Background: The burden of coronavirus disease 2019 (COVID-19) among patients with atopic dermatitis (AD) is poorly understood.

Objectives: The aims of the study were to characterize a large cohort of COVID-19-positive adult patients with AD and to identify predictors of COVID-19-associated hospitalization and mortality.

Methods: A population-based nested case-control study was performed. Multivariable logistic regression was used to evaluate odds ratios and 95% confidence intervals of predictors for COVID-19-associated hospitalization and mortality.

Results: Of 78,073 adult patients with AD, 3618 (4.6%) tested positive for COVID-19. Subclinical COVID-19 infection occurred in 3368 (93.1%) of COVID-19-positive patients, whereas 123 (3.4%), 46 (1.3%), 55 (1.5%), and 26 (0.7%) patients developed a mild, moderate, severe, and critical disease, respectively. Altogether, 250 patients (6.0%) were hospitalized, and 40 patients (1.1%) died because of COVID-19 complications. Coronavirus disease 2019-associated hospitalization was independently associated with the intake of extended courses of systemic corticosteroids (adjusted odds ratio, 1.96; 95% confidence interval, 1.23-3.14; P = 0.005). None of AD-related variables independently predicted COVID-19-associated mortality. The presence of comorbid metabolic syndrome, chronic obstructive pulmonary disease, chronic renal failure, and depression projected both COVID-19-associated hospitalization and mortality.

Conclusions: Prolonged systemic corticosteroids during the pandemic are associated with increased odds of COVID-19-associated hospitalization and should be avoided in patients with AD.
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http://dx.doi.org/10.1097/DER.0000000000000772DOI Listing
October 2021

Is pyoderma gangrenosum associated with solid malignancies? Insights from a population-based cohort study.

Australas J Dermatol 2021 Aug 2;62(3):336-341. Epub 2021 Jun 2.

Clalit Health Services, Tel-Aviv, Israel.

Background: The question of whether solid malignancies (SMs) are associated with pyoderma gangrenosum (PG) remains to be conclusively answered.

Objective: To evaluate the risk of SM among patients with PG and the odds of PG after a diagnosis of SM.

Methods: A population-based retrospective cohort study was conducted to study the risk for SM in patients with PG (n = 302) as compared with age-, sex- and ethnicity-matched control subjects (n = 1799). A case-control design was used to estimate the odds of PG in those with a preexisting history of SM.

Results: The prevalence of a preexisting SM was comparable in patients with PG and controls (7.5% vs. 8.8%, respectively; P = 0.490). The odds of having PG following a diagnosis of a SM was not statistically increased (OR, 0.85; 95% CI, 0.53-1.36). The incidence of SM was 6.8 (95% CI, 3.5-12.2) and 7.9 (95% CI, 6.1-10.1) per 1000 person-years among patients with PG and controls, respectively. Patients with PG were not more likely to develop SM as compared to controls (HR, 0.86; 95% CI, 0.44-1.69). Patients with a dual diagnosis of PG and SM were older and had more frequent comorbid conditions and increased mortality.

Conclusions: SM is not associated with provoking PG, and patients with PG are not at an increased risk of developing SM. A thorough routine screening for SM in patients with new-onset PG is an unnecessary approach based on the study findings.
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http://dx.doi.org/10.1111/ajd.13631DOI Listing
August 2021

Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization and Mortality in Patients with Psoriasis: A Population-Based Study.

Am J Clin Dermatol 2021 Sep 31;22(5):709-718. Epub 2021 May 31.

Clalit Health Services, Tel-Aviv, Israel.

Background: The impact of immune-related conditions on the outcomes of coronavirus disease 2019 (COVID-19) is poorly understood. Determinants of COVID-19 outcomes among patients with psoriasis are yet to be established.

Objective: Th objective of this study was to characterize a large cohort of patients with psoriasis with COVID-19 and to identify predictors of COVID-19-associated hospitalization and mortality.

Methods: A population-based nested case-control study was performed using the computerized database of Clalit Health Services, Israel. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence (CIs) of predictors for COVID-19-associated hospitalization and mortality.

Results: The study population included 3151 patients with psoriasis who tested positive for COVID-19. Subclinical COVID-19 infection occurred in 2818 (89.4%) of the patients while 122 (3.9%), 71 (2.3%), 123 (3.9%), and 16 (0.5%) of the patients experienced a mild, moderate, severe, and critical disease, respectively. Overall, 332 (10.5%) patients were hospitalized and 50 (1.6%) patients died because of COVID-19 complications. Intake of methotrexate independently predicted COVID-19-associated hospitalization (adjusted OR 2.30; 95% CI 1.11-4.78; p = 0.025). Use of biologic agents was not associated with COVID-19-associated hospitalization (OR 0.75; 95% CI 0.32-1.73; p = 0.491) or mortality (OR 0.85; 95% CI 0.12-6.21; p = 0.870). Older age, the presence of comorbid cardiovascular diseases, metabolic syndrome, chronic obstructive pulmonary disease, and chronic renal failure independently predicted both COVID-19-associated hospitalization and mortality.

Conclusions: The use of oral methotrexate was associated with an increased odds of COVID-associated hospitalization, whereas the use of biologic drugs was not associated with worse outcomes of COVID-19 among patients with psoriasis.
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http://dx.doi.org/10.1007/s40257-021-00605-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166379PMC
September 2021

Tumor necrosis factor inhibitors are associated with a decreased risk of COVID-19-associated hospitalization in patients with psoriasis-A population-based cohort study.

Dermatol Ther 2021 07 5;34(4):e15003. Epub 2021 Jun 5.

Clalit Health Services, Tel-Aviv, Israel.

The risk of coronavirus disease 2019 (COVID-19) and its complications among patients with psoriasis treated by tumor necrosis factor inhibitors (TNFis) remains to be decisively delineated. We aimed to assess the risk of COVID-19 infection, COVID-19-associated hospitalization, and mortality among Israeli patients with psoriasis treated by TNFi relative to other systemic agents. A population-based cohort study was conducted to compare psoriasis patients treated by TNFi (n = 1943), with those treated by methotrexate (n = 1929), ustekinumab (n = 348), and acitretin (n = 1892) regarding COVID-19 outcomes. Risk of investigated outcomes was assessed using uni- and multi-variate Cox regression analyses. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality in the TNFi group was 35.8 (95% CI, 26.1-47.9), 0.8 (95% CI, 0.0-4.2), and 0.0 per 1000 person-years, respectively. Exposure to TNFi was associated with a comparable risk of COVID-19 infection [adjusted hazard ration (HR) for TNFi vs methotrexate: 1.07 (95% CI, 0.67-1.71); TNFi vs ustekinumab: 1.07 (95% CI, 0.48-2.40); TNFi vs acitretin: 0.98 (95% CI, 0.61-1.57)]. TNFi was associated with a decreased risk of COVID-19-associated hospitalization relative to methotrexate (adjusted HR, 0.10; 95% CI, 0.01-0.82) and ustekinumab (adjusted HR, 0.04; 95% CI, 0.00-0.64), but not to acitretin (adjusted HR, 1.00; 95% CI, 0.16-6.16). No significant difference in COVID-19-associated mortality was found between the four different groups. TNFi was associated with a decreased risk of admissions due to COVID-19. Our findings substantiate the continuation of TNFi treatment during the pandemic. TNFi may be positively considered in patients with moderate-to-severe psoriasis warranting systemic treatment during the pandemic.
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http://dx.doi.org/10.1111/dth.15003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209905PMC
July 2021

Survival of Adjuvant Drugs for Treatment of Pemphigus: A Population-based Cohort Study.

Acta Derm Venereol 2021 Sep 3;101(9):adv00535. Epub 2021 Sep 3.

Lübeck Institute of Experimental Dermatology , University of Lübeck, Ratzeburger Allee 160, DE-23562 Lübeck, Germany. E-mail:

Drug survival reflects the real-life efficacy and safety of therapeutic agents. Evidence regarding the durability of adjuvant agents in the treatment of pemphigus is sparse. The aims of this study were to investigate the survival of adjuvant agents used to manage patients with pemphigus, and to identify predictors of treatment dropout. A retrospective population-based cohort study was designed to follow patients with pemphigus managed by adjuvant agents. The study population included 436 patients with pemphigus managed by 608 adjuvant agent courses. The highest median drug survival time was observed for rituximab (43.6 months, 95% confidence interval (95% CI) 5.3-81.9), followed by cyclophosphamide (30.5 months; 95% CI 10.5-50.5), azathioprine (22.9 months; 95% CI 15.6-30.2), and mycophenolate mofetil (20.2 months; 95% CI 10.0-30.4). Compared with azathioprine, cyclosporine (adjusted hazard ratio 2.98; 95% CI 1.57-5.62; p = 0.005) and dapsone (adjusted hazard ratio 1.83; 95% CI 1.07-3.15; p = 0.027) were associated with a significantly increased risk of drug discontinuation. To conclude, rituximab, azathioprine, and mycophenolate mofetil demonstrated better durability, whilst dapsone and cyclosporine were associated with low drug survival and high dropout.
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http://dx.doi.org/10.2340/00015555-3831DOI Listing
September 2021

Hepatitis B and C among patients with hidradenitis suppurativa: a population-based study.

Int J Dermatol 2021 May 17. Epub 2021 May 17.

Department of Quality Measures and Research, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory condition related to multiple systemic diseases and infections.

Methods: This retrospective cross-sectional study from 1999 to 2015 used the database of Clalit Health Services, the largest managed care organization in Israel, to explore the association between HS and hepatitis B and C. Sociodemographic and clinical information was compared using χ tests for sex and socioeconomic status and t-tests for age. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to compare the odds of hepatitis B and C in those with and without HS.

Results: In multivariate analysis controlling for sex, age as a continuous variable, Arab ancestry, and history of drug abuse, HS was associated with a 1.87-fold increased odds (95% CI 1.11-3.17, P = 0.019) of hepatitis B (HBV). HS was also associated with HCV in multivariate analysis controlling for sex, age per year, Arab ancestry, alcohol use, and drug use, with a 1.74-fold increased odds (95% CI 1.05-2.89, P = 0.032) of hepatitis C (HCV) among those with HS as compared to controls.

Conclusions: This study demonstrated an association between HS and both hepatitis B and hepatitis C.
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http://dx.doi.org/10.1111/ijd.15578DOI Listing
May 2021

Mortality in Ankylosing Spondylitis According to Treatment: A Nationwide Retrospective Cohort Study of 5900 Patients from Israel.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.

Objectives: In this large population-based study we aimed to assess:(1)mortality in ankylosing-spondylitis(AS) patients compared to the general population.Considering demographics,comorbidities and treatment.(2)factors associated with mortality within AS patients.

Methods: This study was designed as a retrospective-cohort study utilizing the electronic-database of the largest health maintenance organization in Israel.All AS patients diagnosed between 2002-2018 were included.Controls were matched by age,gender,clinic, and enrollment-time.Follow-up continued until death or end of study.

Results: The study comprised 5,930 AS patients and 29,018 matched controls that were followed-up for a median period of 7.5 years.There were 667 deaths within the AS cohort and 2,919 deaths within controls,the mean age-at-death was 76.9 years and 77.1 years respectively(p=0.74). 3,249(55.8%) of AS patients were treated only with non-steroidal-anti-inflammtory-drugs(NSAIDs), 1,760(30.2%) were treated with tumor-necrosis-factor-α-inhibitors(TNFi),and 1,687(29.0%) with disease-modifying-antirheumatic-drugs(DMARDs).Mortality rates were increased among AS patients compared to controls with an age-and-sex-adjusted HR of 1.19(95%CI1.10-1.30).The association was significant for men(HR=1.15,95%CI 1.04-1.27) and women(HR=1.32,95%CI 1.13-1.54), and after adjusting for background comorbidities (HR=1.14,95%CI 1.05-1.24).AS patients treated with TNFi or with a combination of TNFi and DMARDs did not have significant difference in mortality rates compared to controls(HR=0.67,95%CI 0.38-1.18;HR=0.93,95%CI 0.69-1.25;respectively).Age,male-gender,mean C-reactive-protein(CRP) levels and general comorbidities were predictors of mortality within the AS cohort.

Conclusion: AS patients had increased mortality risk compared to the general population after adjusting for age, sex, and baseline comorbidities.AS patients treated with TNFi did not demonstrate excess mortality compared to matched controls.Within the AS cohort age, male-gender, background comorbidities, and higher CRP levels were identified as risk factors for mortality.
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http://dx.doi.org/10.1002/acr.24616DOI Listing
May 2021

Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis-A Cross-Sectional Study.

Int J Environ Res Public Health 2021 04 10;18(8). Epub 2021 Apr 10.

Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON M3J 1P3, Canada.

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case-control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student's t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan-Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy ( = 48 [2.3%]) as compared to controls ( = 141 [1.4%], < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.
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http://dx.doi.org/10.3390/ijerph18083983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068784PMC
April 2021

Chronic renal comorbidities in pyoderma gangrenosum: a retrospective cohort study.

Immunol Res 2021 06 22;69(3):249-254. Epub 2021 Apr 22.

Clalit Health Services, Tel-Aviv, Israel.

The coexistence of pyoderma gangrenosum (PG) and chronic renal comorbidities has been reported anecdotally. We aimed to assess the bidirectional association between PG and the following chronic renal comorbidities: chronic renal failure (CRF), dialysis, kidney transplantation (KT), and other kidney diseases (OKD). That is to evaluate (i) the risk of the aforementioned diseases among patients with PG (ii) and the odds of PG after a diagnosis of renal comorbidities. A population-based retrospective cohort study was conducted comparing PG patients (n=302) with age-, sex-, and ethnicity-matched control subjects (n=1497) with regard to incident cases of renal comorbidities. A case-control design was additionally adopted to estimate the odds of PG in those with a preexisting history of renal comorbidities. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. Patients with PG demonstrated an increased risk of CRF (adjusted HR, 3.68; 95% CI, 2.72-5.97), dialysis (adjusted HR, 27.79; 95% CI, 3.24-238.14), and OKD (adjusted HR, 2.71; 95% CI, 1.55-4.74). In addition, the odds of PG were increased after the diagnosis of CRF (adjusted OR, 2.34; 95% CI, 1.33-4.11), KT (adjusted OR, 5.03; 95% CI, 1.01-25.12), and OKD (adjusted OR, 1.69; 95% CI, 1.04-2.74). Patients with a dual diagnosis of PG and renal diseases presented with PG at an older age and had a higher prevalence of comorbid conditions. In conclusion, a bidirectional association exists between PG and chronic renal conditions. Awareness of this comorbidity may be of benefit for physicians managing patients with PG.
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http://dx.doi.org/10.1007/s12026-021-09187-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266709PMC
June 2021

Atopic Dermatitis and Infertility: A Nationwide Retrospective Cohort Study.

Dermatology 2021 Apr 21:1-7. Epub 2021 Apr 21.

Siaal Research Center for Family Medicine and Primary Care, Division of Community Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Background: Given that common pathophysiological factors play a role in atopic dermatitis (AD) and infertility, we assumed that the 2 conditions might demonstrate an epidemiological association. Large-scale epidemiological data on this topic are lacking.

Objectives: The aim of this work was to evaluate the potential association between AD and infertility in a broad community-based population.

Methods: A nationwide retrospective cohort study was conducted, analyzing the association between AD and infertility. We compared AD patients diagnosed by a dermatologist between 2002 and 2018 and a matched control group. The study population was subdivided according to age into adults (age ≥18 years) and children (age <18 years), and was further subdivided according to AD severity, classified as either mild or moderate-to-severe according to AD-related drug use and healthcare services utilization.

Results: The study included 127,150 patients with AD and 127,071 comparison enrollees. AD was associated with a higher prevalence of infertility than that of the control group (1.4 and 1.1%, respectively). The prevalence of infertility, per 1,000 patient-years, was increased in patients with AD compared to that of the control group (2.17 and 1.7, respectively). Multivariate analysis for infertility demonstrated that AD was a key risk factor for infertility in both males and females with mild AD and moderate-to-severe AD.

Conclusion: A significant association between AD and infertility was observed. This association suggests that infertility may be an additional manifestation of AD. Further studies are warranted to evaluate the impact of AD management in the setting of infertility and vice versa.
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http://dx.doi.org/10.1159/000515600DOI Listing
April 2021

Risk of COVID-19 Infection, Hospitalization, and Mortality in Patients with Psoriasis Treated by Interleukin-17 Inhibitors.

J Dermatolog Treat 2021 Mar 24:1-28. Epub 2021 Mar 24.

Clalit Health Services, Tel-Aviv, Israel.

Background: The risk of the infection and its complications under this drug class remains to be determined.

Objective: To evaluate the risk of COVID-19, COVID-19-associated hospitalization, and mortality among patients with psoriasis treated by IL-17I.

Methods: A population-based cohort study was performed to compare psoriasis patients treated by IL-17I (n = 680) with those treated by methotrexate (n = 2,153) and non-systemic/non-immunomodulatory treatments (n = 138,750) regarding the incidence of COVID-19 and its complications.

Results: The use of IL-17I was not associated with an increased risk of COVID-19 infection [adjusted HR for IL-17I vs. methotrexate: 0.91 (95% CI, 0.48-1.72); IL-17I vs. non-systemic/non-immunomodulatory treatments: 0.92 (95% CI, 0.54-1.59)]. IL-17I was associated with comparable risk of COVID-19-associated hospitalization [adjusted HR for IL-17I vs. methotrexate: 0.42 (95% CI, 0.05-3.39); IL-17I vs. non-systemic/non-immunomodulatory treatments: 0.65 (95% CI, 0.09-4.59)] and COVID-19-associated mortality [adjusted HR for IL-17I vs. methotrexate: 7.57 (95% CI, 0.36-157.36); IL-17I vs. non-systemic/non-immunomodulatory treatments: 7.05 (95% CI, 0.96-51.98)]. In a sensitivity analysis, neither secukinumab nor ixekizumab imposed an elevated risk of any of the outcomes of interests.

Conclusions: IL-17I treatment does not confer an increased risk of COVID-19 infection or its complications in patients with psoriasis. Our findings support the continuation of IL-17I treatment during the pandemic.
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http://dx.doi.org/10.1080/09546634.2021.1905766DOI Listing
March 2021

The risk of COVID-19 in patients with bullous pemphigoid and pemphigus: A population-based cohort study.

J Am Acad Dermatol 2021 07 17;85(1):79-87. Epub 2021 Mar 17.

Clalit Health Services, Tel-Aviv, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Background: The burden of COVID-19 in patients with bullous pemphigoid (BP) and pemphigus is yet to be evaluated.

Objective: To assess the risks of COVID-19 and COVID-19-associated hospitalization and mortality in patients with BP and pemphigus and to delineate determinants of severe COVID-19 illness among these patients.

Methods: A population-based cohort study compared COVID-19 and its complications in patients with BP (n = 1845) and pemphigus (n = 1236) with age-, sex-, and ethnicity-matched control subjects.

Results: The risks of COVID-19 (hazard rate [HR], 1.12; 95% confidence interval [CI], 0.72-1.73; P = .691) and COVID-19-associated hospitalization (HR, 1.58; 95% CI, 0.84-2.98; P = .160) was comparable between patients with BP and controls. The risk of COVID-19-associated mortality was higher among patients with BP (HR, 2.82; 95% CI, 1.15-6.92; P = .023). The risk of COVID-19 (HR, 0.81; 95% CI, 0.44-1.49; P = .496), COVID-19-associated hospitalization (HR, 1.41; 95% CI, 0.53-3.76; P = .499), and COVID-19-associated mortality (HR, 1.33; 95% CI, 0.15-11.92; P = .789) was similar in patients with pemphigus and their controls. Systemic corticosteroids and immunosuppressants did not predispose COVID-19-positive BP and pemphigus patients to a more severe illness.

Limitations: Retrospective data collection.

Conclusions: Patients with BP experience increased COVID-19-associated mortality and should be monitored closely. Maintaining systemic corticosteroids and immunosuppressive adjuvant agents during the pandemic is not associated with worse outcomes.
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http://dx.doi.org/10.1016/j.jaad.2021.02.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968167PMC
July 2021

Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study.

Arch Dermatol Res 2021 Mar 9. Epub 2021 Mar 9.

Clalit Health Services, Tel-Aviv, Israel.

The association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case-control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14-2.06). This risk was higher among males (OR 1.66; 95% CI 1.09-2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11-2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14-2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73-1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.
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http://dx.doi.org/10.1007/s00403-021-02211-4DOI Listing
March 2021

Estimating the Odds of Ulcerative Colitis-Associated Pyoderma Gangrenosum: A Population-Based Case-Control Study.

Dermatology 2021 1;237(3):323-329. Epub 2021 Mar 1.

Clalit Health Services, Tel-Aviv, Israel.

Background: Ulcerative colitis (UC) is a well-known underlying comorbidity of pyoderma gangrenosum (PG). However, the risk conferred by UC for the subsequent development of PG is yet to be elucidated. We aimed to estimate the magnitude of the association between UC and the subsequent occurrence of PG, which would enable us to assess the odds of PG developing in individuals with a history of UC.

Methods: A population-based case-control study was conducted to compare PG patients (n = 302) and age-, sex- and ethnicity-matched control subjects (n = 1,497) regarding the presence of UC. Logistic regression models were utilized for univariate and multivariate analyses.

Results: The prevalence of preexisting UC was greater in patients with PG than in controls (7.3 vs. 0.5%; p < 0.001). A 15-fold increase in the odds of PG in individuals with preexisting UC was observed (OR 14.62, 95% CI 6.45-33.18). The greatest risk of developing PG occurred in the first years following the diagnosis of UC (OR 35.50, 95% CI 4.35-289.60), and decreased thereafter to 10.03 (95% CI 1.83-55.03), 6.69 (95% CI 1.49-30.02), and 10.03 (95% CI 1.83-55.03) at 1-5, 5-10, and 10-15 years after the diagnosis of UC, respectively. This association retained its statistical significance following the adjustment for confounding factors (adjusted OR 10.78, 95% CI 4.55-25.52). Patients with both PG and UC were younger and had a lower prevalence of smoking than the remaining patients with PG.

Conclusions: UC increases the odds of developing PG by 15-fold, with the highest probability of developing PG occurring within the first year after the diagnosis of UC. Patients with UC may be advised to avoid additional precipitating factors for the development of PG.
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http://dx.doi.org/10.1159/000512931DOI Listing
March 2021

A History of Asthma Increases the Risk of Bullous Pemphigoid: Insights from a Large Population-Based Study.

Dermatology 2021 Feb 26:1-8. Epub 2021 Feb 26.

Clalit Health Services, Tel-Aviv, Israel.

Background: Bullous pemphigoid (BP) and asthma both share a pathogenic role of eosinophils and immunoglobulin E (IgE) and favorable response for corticosteroids and omalizumab. However, the association between these conditions is yet to be investigated. We sought to estimate the risk of having BP among patients previously diagnosed with asthma and to characterize patients with coexistent BP and asthma.

Methods: Utilizing the dataset of Clalit Health Services, a population-based case-control study was conducted comparing BP patients (n = 3,924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280) regarding the presence of asthma. Logistic regression models were utilized for univariate and multivariate analyses.

Results: The prevalence of preceding asthma was higher in patients with BP than in control subjects (11.1 vs. 7.9%, respectively; p < 0.001). A history of asthma was associated with a 50% increase in the risk of BP (OR 1.45; 95% CI 1.30-1.62). The association was not altered greatly after adjusting for demographics (adjusted OR 1.43; 95% CI 1.28-1.61) as well as for demographics and comorbidities (adjusted OR 1.40; 95% CI 1.25-1.57). The average (SD) latency between the diagnosis of asthma and the development of BP was 12.5 (14.7) years. When compared with other patients with BP, those with a dual diagnosis of BP and asthma were older, had higher BMI, and were more frequently managed by corticosteroids and immunosuppressive and immunomodulatory adjuvants.

Conclusions: Asthma confers a predisposition to the development of BP. Awareness of this association may be of help for physicians managing patients with BP and asthma. Further research is required to elucidate the mechanism underlying this observation.
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http://dx.doi.org/10.1159/000512917DOI Listing
February 2021

Familial Mediterranean Fever and Asthma.

Rheumatology (Oxford) 2021 Feb 16. Epub 2021 Feb 16.

Department of Medicine 'B'. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.

Objective: To assess the association between familial Mediterranean fever and asthma.

Methods: This study was designed as a cross-sectional study. All patients diagnosed with familial Mediterranean fever between January 1, 2000, to December 31, 2016, who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status, and country of birth. Logistic regression models were used to determine the odds ratio for asthma in familial Mediterranean fever patients and controls.

Results: A total of 7,098 familial Mediterranean fever patients who were prescribed colchicine were identified. Of them, 3,547 (50%) were females, 3,632 (51%) were of low residential socioeconomic status and 6,160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23-54). In an unadjusted logistic regression, familial Mediterranean fever was associated with asthma (OR = 1.33, 95%CI 1.17-1.51; p < 0.001). The association persisted after adjusting for sex, socioeconomic status, and country of birth (OR = 1.33, 95%CI 1.18-1.52; p < 0.001).

Conclusions: Familial Mediterranean fever is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying familial Mediterranean fever to be a protective factor from asthma.
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http://dx.doi.org/10.1093/rheumatology/keab159DOI Listing
February 2021

Risk of solid malignancies in bullous pemphigoid: A large-scale population-based cohort study.

J Dermatol 2021 Mar 28;48(3):317-323. Epub 2020 Dec 28.

Clalit Health Services, Tel Aviv, Israel.

The association of bullous pemphigoid (BP) with solid malignancies (SM) is a matter of controversy, as previous studies produced inconclusive findings. The aim of this study was to assess the risk of SM among patients with BP and to evaluate whether a history of SM predisposes individuals to develop subsequent BP. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and race-matched control subjects (n = 19 280) with regard to incident cases of SM. Adjusted hazard ratios (HR) and adjusted odds ratios (OR) were estimated by Cox regression and logistic regression, respectively. The incidence of SM was 13.4 (95% confidence interval [CI], 11.6-15.3) and 14.3 (95% CI, 13.5-15.1) per 1000 person-years among patients with BP and controls, respectively. BP was not associated with an increased risk of SM (adjusted HR, 0.90; 95% CI, 0.77-1.05). Additionally, a history of SM was not related to the risk of subsequent BP (adjusted OR, 1.00; 95% CI, 0.90-1.10). In a stratified analysis, patients with BP had an increased risk of uterine cancer (adjusted HR, 2.56; 95% CI, 1.39-4.72) unlike the 18 remaining analyzed types of SM. Relative to BP patients without SM, those with BP and SM were older, had a male predominance, a higher prevalence of smoking, a higher burden of comorbidities and comparable survival rates. Although patients with BP do not experience an overall increased risk of developing SM, they are more likely to have uterine cancer. Our findings argue against routine extended cancer screening for patients with incident BP, but raise the awareness of uterine cancer among females with BP.
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http://dx.doi.org/10.1111/1346-8138.15685DOI Listing
March 2021

Acne keloidalis nuchae and thyroid diseases: a population-based cohort study.

Int J Dermatol 2021 Apr 10;60(4):466-470. Epub 2020 Dec 10.

Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Background: The association between acne keloidalis nuchae (AKN) and thyroid diseases is yet to be investigated.

Objective: To evaluate the risk of developing hypothyroidism and hyperthyroidism among patients with AKN and to characterize the patients who have AKN and thyroid comorbidities.

Methods: A population-based cohort study was conducted comparing AKN patients (n = 2,677) with age-, gender-, and ethnicity-matched control subjects (n = 13,190) with regard to incident cases of hypothyroidism and hyperthyroidism. Adjusted hazard ratios (HRs) were estimated by Cox regression analysis.

Results: The incidence rates of hypothyroidism among patients with AKN and controls were estimated at 2.15 (95% CI, 1.49-2.99) and 0.82 (95% CI, 0.66-1.00) cases/1000 person-years, respectively. The crude risk of developing incident hypothyroidism was 1.85-fold greater in patients with AKN (HR, 1.85; 95% CI, 1.24-2.78; P = 0.003). The elevated risk persisted following the adjustment for putative confounders (adjusted HR, 1.72; 95% CI, 1.03-2.89; P = 0.040). The risk of hyperthyroidism was comparable in patients with AKN and controls both in the crude (HR, 1.55; 95% CI, 0.57-4.22) and adjusted (adjusted HR, 1.92; 95% CI, 0.59-6.21) analyses. Patients with coexistent AKN and thyroid diseases were significantly older at the onset of AKN, had more prominent female preponderance, and had a higher burden of comorbidity.

Conclusions: Patients with AKN are at an increased risk of hypothyroidism. Screening for hypothyroidism should be considered in AKN patients with a compatible clinical picture.
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http://dx.doi.org/10.1111/ijd.15331DOI Listing
April 2021

Dysthyroidism in dermato/polymyositis patients: A case-control study.

Eur J Clin Invest 2021 May 20;51(5):e13460. Epub 2020 Dec 20.

Department of Medicine 'B', The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.

Background: Dermatomyositis (DM) and polymyositis (PM) are two rare autoimmune disorders occasionally described with dysthyroidism; however, no solid evidence still proves such an association.

Aim: To evaluate the prevalence of dysthyroidism among DM/PM patients.

Design And Setting: A nation-wide case-control study was conducted.

Methods: From the Clalit Health Services health records database, we extracted 2085 (DM = 1475 (70.7%), PM = 610 (29.3%)) PM/DM cases and 10 193 sex-age matched controls in the period 2000-2018. Both univariate and multivariate analyses were performed to evaluate the link dysthyroidism and PM/DM. Survival analysis was also performed.

Results: The rate of hyperthyroidism was significantly (P = .0097) higher in cases (n = 40, 1.9%) with respect to controls (n = 123, 1.2%). Similarly, the rate of hypothyroidism was significantly (P < .0001) associated with cases (n = 234, 11.2%) when compared to controls (n = 853, 8.4%). At the multivariate logistic regression analysis, both DM (OR 1.31 [95%CI 1.07-1.60], P = .0087) and PM (OR 1.54 [95%CI 1.21-1.95], P = .004) were significantly associated with hypothyroidism, whereas DM (OR 1.70 [95%CI 1.10-2.61], P = .0165) but not PM (OR 1.45 [0.83-2.55], P = .1947) was found to be associated with hyperthyroidism. Subjects with PM and positive for anti-Sjögren's syndrome-related antigen A (SSA) auto-antibody displayed a significant risk of developing hyperthyroidism (OR 5.85 [95%CI 1.02-33.74], P = .0480), whereas individuals with DM and positive for antinuclear antibody (ANA) had a higher risk of developing hyperthyroidism (OR 2.65 [95%CI 1.00-7.03], P = .0498).

Conclusions: Physicians treating PM/DM patients should consider screening for thyroid dysfunction on a regular basis.
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http://dx.doi.org/10.1111/eci.13460DOI Listing
May 2021

Hidradenitis suppurativa is associated with hypothyroidism and hyperthyroidism: a large-scale population-based study.

Int J Dermatol 2021 Mar 25;60(3):321-326. Epub 2020 Nov 25.

Department of Quality Measurements and Research, Chief Physician Office, Clalit Health Services, Tel Aviv, Israel.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving the skin bearing apocrine glands. There are numerous comorbidities and associated diseases among patients with HS. The association of HS and thyroid abnormalities is equivocal. We aimed to explore whether HS is associated with thyroid disorders.

Methods: In this cross-sectional large-scale population-based study in Israel, patients with a validated diagnosis of HS were matched at a proportion of 1:5 with age- and gender-matched healthy controls without HS. A cross-checking for HS diagnosis by International Classification of Diseases, ninth revision (ICD-9) coding, and hyperthyroidism and hypothyroidism by ICD-9 coding was performed. Demographic and exposure covariates were identified. Univariate and multivariate logistic regressions were utilized to establish the association of HS with thyroid disorders.

Results: Study participants included 4,191 HS patients and 20,941 controls. The average age of patients was 39.7 years old, and 61.8% were female. 53.4% of HS patients and 13.5% of controls (P < 0.001) were smokers. Odds ratios (ORs) for hypothyroidism and hyperthyroidism in HS were 2.91 (95% confidence interval [CI] 2.48-3.40) and 2.25 (95% CI 1.55-3.28), respectively (P < 0.001 for both). While the association of HS with hypothyroidism was maintained across genders and all age groups, and remained positive after controlling for smoking status, the association with hyperthyroidism remained positive only among females, middle-aged patients, and nonsmokers.

Conclusion: HS is independently associated with hypothyroidism. The association of HS with hyperthyroidism held significance only in limited subgroups. Smoking status is a major modifier, mainly in the association of HS with hyperthyroidism.
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http://dx.doi.org/10.1111/ijd.15319DOI Listing
March 2021

Coping with Psoriasis or Hidradenitis Suppurativa: A Qualitative Study.

Adv Skin Wound Care 2020 Dec;33(12):662-668

Shani Fisher, MA, RN, is Chief Nurse, Dermatology Clinic, Emek Medical Center, Afula, and PhD student, Nursing Department, Steyer School of Health Professions, Sackler School of Medicine, Tel Aviv University, Israel. Moriah Ellen, PhD, is Senior Lecturer and Investigator, Department of Health Systems Management, Guilford Glazer Faculty of Business and Management and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Arnon D. Cohen, MD, is dermatologist and Head of Department of Quality Measurements and Research, Chief Physician's Office, Clalit Health Services, Tel Aviv. Ilya Kagan, PhD, RN, is Senior Lecturer, Nursing Department, Steyer School of Health Professions, Sackler School of Medicine, Tel Aviv University. The authors have disclosed no financial relationships related to this article. Submitted September 28, 2019; accepted in revised form December 12, 2019.

Objective: Psoriasis and hidradenitis suppurativa (HS) are both chronic inflammatory skin diseases with significant comorbidity. This study aimed to examine how patients with psoriasis or HS cope with their conditions on a personal and psychosocial level, especially in times of clinical exacerbation and symptom deterioration.

Design: This qualitative initial study used the phenomenology model to examine patients' lived experiences through the lens of their disease. Via semistructured interviews and content analysis, researchers aimed to describe the subjective reality of people with HS or psoriasis and identify any common issues.

Patients And Intervention: Six open pilot interviews with three patients with HS and three patients with psoriasis uncovered five cardinal domains affecting patients' lives. After completing all the interviews, transcripts were analyzed and classified numerically by frequency of identified terms and keywords. After classifications and data ranking, the main issues were identified and separated into the five domains.

Main Results: Researchers interviewed 20 patients (10 with psoriasis and 10 with HS). The five domains were distressing symptoms, struggling to cope with the disease, avoiding acute or recurrent eruptions, dealing with eruption, and information sources regarding the disease. Pain and pruritus were the most disturbing symptoms, and the remaining issues concerned the emotional, functional, and financial burden of these chronic conditions.

Conclusions: Even though the symptoms of HS and psoriasis are different, this study reveals common denominators regarding the emotional side of living with chronic skin disease.
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http://dx.doi.org/10.1097/01.ASW.0000720260.58886.08DOI Listing
December 2020

Patients with pemphigus are at an increased risk of developing rheumatoid arthritis: a large-scale cohort study.

Immunol Res 2020 12 7;68(6):373-378. Epub 2020 Nov 7.

Clalit Health Services, Tel-Aviv, Israel.

Data regarding the association between pemphigus and rheumatoid arthritis (RA) is inconclusive and yet to be firmly established. In the current study, we aimed to evaluate the risk of developing RA during the course of pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the hazard ratio (HR) of RA among 1985 patients with pemphigus relative to 9874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of RA was 1.07 (95% CI, 0.62-1.72) and 0.36 (95% CI, 0.24-0.52) per 1000 person-years among patients with pemphigus and controls, respectively. The lifetime prevalence of RA was 2.3% (95% CI, 1.7-3.1%) among cases and 1.8% (95% CI, 1.5-2.0%) among controls. Patients with pemphigus were more than twice as likely to develop RA as compared to control subjects (adjusted HR, 2.54; 95% confidence interval [CI], 1.31-4.92). The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted HR, 2.56; 95% CI, 1.30-5.05). In conclusion, pemphigus is associated with an increased risk of RA. Physicians treating patients with pemphigus should be aware of this possible association. Further research is required to better understand the mechanism underlying this association.
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http://dx.doi.org/10.1007/s12026-020-09160-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674560PMC
December 2020
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