Journal Article Annotations
2021, 1st Quarter

Psychodermatology

Annotations by J. Jewel Shim, MD
March, 2021

Protective Effects of Anti-depressants against the Subsequent Development of Psoriasis in Patients with Major Depressive Disorder: a Cohort Study.
Suicidal risks with psoriasis and atopic dermatitis: Systematic review and meta-analysis.
Atopic Dermatitis and Dementia Risk: A Nationwide Longitudinal Study.

- Posttraumatic stress disorder and the associated risk of autoimmune skin diseases: A nationwide population-based cohort study

PUBLICATION #1 — Psychodermatology

Protective Effects of Anti-depressants against the Subsequent Development of Psoriasis in Patients with Major Depressive Disorder: a Cohort Study.

Ya-Mei Tzeng, I-Hsun Li, Hui-Han Kao, Jui-Hu Shih, Chin-Bin Yeh, Yi-Hsien Chen, Li-Ting Kao

Abstract: J Affect Disord. 2021 Feb 15;281:590-596. doi: 10.1016/j.jad.2020.11.110. Epub 2020 Nov 21.

Background:
Inflammation may mediate the relationship between major depressive disorder (MDD) and psoriasis. However, it is unclear whether anti-depressants can decrease the subsequent risk of psoriasis among MDD patients. This study investigated the effects of anti-depressants on the subsequent risk of psoriasis in MDD patients.

Methods:
This was a population-based cohort study in Taiwan. 58,454 MDD patients who had received anti-depressants and 6,034 MDD patients who did not receive anti-depressants were included. Each patient was tracked for 5 years to confirm a diagnosis of psoriasis following the index date. Cox proportional hazards models were performed to estimate the hazard ratio (HR) for psoriasis.

Results:
In this study, after using time-dependent Cox regression with both inverse probability of treatment weighting (IPTW) and adjustment for confounders, anti-depressant users had a significantly lower risk of psoriasis than the nonusers (IPTW-adjusted HR [aHR] = 0.69). Additionally, most types and dosages of anti-depressants tended to protect against psoriasis. Selective serotonin reuptake inhibitor use (IPTW-aHR = 0.67) and low-dose anti-depressant use (IPTW-aHR = 0.66) had significant protective effects even after IPTW and adjustment for confounders.

Limitations:
This study had no information about over-the-counter medications.

Conclusions:
This study revealed the protective effects of anti-depressants on psoriasis risk in patients with MDD. Antidepressant users had significantly lower risk of psoriasis than the nonusers. Further analyses indicated that the usage of SSRIs and low antidepressant dosage could statistically decrease risk of psoriasis.

Annotation

The finding:
Previous studies have established an association between major depressive disorder (MDD) and inflammation-mediated medical conditions such as cardiovascular disease and diabetes as well as certain inflammatory skin conditions, such as psoriasis. Some studies have posited that the relationship between depression and psoriasis may be bidirectional, while other study results have suggested that MDD may contribute to the onset of psoriasis. Moreover, there is also evidence that the use of antidepressants may mitigate inflammatory markers found in depression. The study investigators sought to examine whether this effect could extend to reducing the risk of developing psoriasis in a cohort of subjects with MDD treated with antidepressants.

Strength and weaknesses:
Strengths include large study size and longitudinal follow up, meticulous confirmation of an MDD diagnosis, and matched control group. The study authors used inverse probability of treatment weighting (IPTW) to minimize bias of comorbid inflammatory conditions and utilized time dependent statistical analyses (Cox proportional hazards) that could better establish a temporal relationship between antidepressant use and subsequent diagnosis (or lack thereof) of psoriasis. One major weakness is that the study did not account for the use of over-the-counter medications that could have affected the results. The generalizability of the results was also highlighted as a limitation, as the study subjects were almost exclusively drawn from one major ethnic group.

Relevance:
This is an interesting study that highlights the scope of the potential benefits of treatment with antidepressants in not only treating depression but also mitigating the development of other inflammation-mediated disease.

Type of study (EBM guide):
Cohort study

PUBLICATION #2 — Psychodermatology

Suicidal risks with psoriasis and atopic dermatitis: Systematic review and meta-analysis.

Maurizio Pompili, Luca Bonanni, Flavia Gualtieri, Giada Trovini, Severino PersechinoRoss J Baldessarini

Abstract: J Psychosom Resj.jpsychores.2020.110347. Epub 2020 Dec 26.

Objective:
Evidence of increased suicidal risk in association with psoriasis is growing, but findings concerning atopic dermatitis are inconsistent.

Methods:
We systematically reviewed reports of suicidal ideation, attempts, or suicides among subjects diagnosed with psoriasis or atopic dermatitis compared to healthy controls or persons with other illnesses. Reported rates of suicidal ideation and behavior were compared among the groups, using meta-analyses to compare suicidal rates with dermatologic patients versus controls, as well as between dermatological diagnoses.

Results:
Mean rates of suicidal ideation with psoriasis were 1.60-fold (13.9%/8.67%) above controls, and with atopic dermatitis, 1.84-fold higher (16.8%/9.12%); meta-analyses found similar differences: psoriasis (OR = 1.97 [CI: 1.26-3.08]; p = 0.003) and atopic dermatitis (OR = 2.62 [1.32-5.19]; p = 0.006). For suicidal acts, with psoriasis, mean rates versus controls were 2.51-fold higher (3.34%/1.33%), and 2.81-fold higher (5.03%/1.79%) with atopic dermatitis; meta-analyses found significantly more suicidal acts with psoriasis (OR = 1.42 [1.05-1.92]; p = 0.02) and a similar tendency with atopic dermatitis (OR = 1.53 [0.96-2.45]; p = 0.08).

Conclusions:
The study findings support emerging evidence of increased risk of suicidal ideation and behavior with psoriasis and extend it to increased risk of suicidal ideation and a trend toward increased suicidal acts with atopic dermatitis.

Keywords:
Atopic dermatitis; Attempt; Depression; Ideation; Inflammation; Psoriasis; Suicide.

Annotation

The finding:
Psoriasis and atopic dermatitis are immune-mediated, inflammatory dermatological disorders that have known psychosocial burdens and have been associated with depression. Suicidal thoughts, depression, and other psychiatric disorders have also been associated with systemic inflammation. Given these associations and prior studies suggesting a relationship between these skin disorders and suicidal thoughts and behaviors, this systematic review examined the rate of suicidal ideation and behavior among patients with psoriasis and atopic dermatitis compared to control subjects. The study authors found that psoriasis was significantly associated with higher rates of suicidal ideation and behaviors, while atopic dermatitis was only significantly linked to suicidal ideation, with a trend toward an association with suicidal behaviors.

Strength and weaknesses:
This study is a meta-analysis, but included studies were small and thus limited power. There was limited information regarding criteria for psychiatric diagnoses or substance us disorders that may have been associated with suicidal ideation/behaviors.

Relevance:
Awareness of the association between these immune system mediated skin disorders and suicidal thoughts/behaviors may guide C-L psychiatrists in their treatment planning and recommendations to consulting teams.

Type of study (EBM guide):
Systematic review or meta-analysis

PUBLICATION #3 — Psychodermatology

Atopic Dermatitis and Dementia Risk: A Nationwide Longitudinal Study.

Tai-Long Pan, Ya-Mei Bai, Chih-Ming Cheng, Shih-Jen Tsai, Chia-Fen Tsai, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Tzeng-Ji Chen, Chih-Sung Liang, Mu-Hong Chen

Abstract: Ann Allergy Asthma Immunol. 2021 Mar 11;S1081-1206(21)00177-0. doi: 10.1016/j.anai.2021.03.001. Online ahead of print.

Background:
Retrospective studies have suggested that patients with dementia have higher atopic dermatitis (AD) prevalence than do those without dementia.

Objective:
However, the temporal association of AD with subsequent dementia remains unknown.

Methods:
We included data of patients with AD aged ≥45 years (n = 1,059) and 1:10 age, sex, residence, income, and dementia-related comorbidity-matched controls (n =10,590) from the Taiwan National Health Insurance Research Database and reviewed their subsequent dementia development from the enrollment date to the end of 2013.

Results:
After adjustments for dementia-related comorbidities, patients with AD were found to be more likely to develop any dementia (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.24-3.29), particularly Alzheimer’s disease (HR: 3.74, 95% CI: 1.17-11.97), during the follow-up period than were those in the control group. Moderate-to-severe AD was associated with a high subsequent dementia risk (HR: 4.64, 95% CI: 2.58-8.33). Sensitivity analyses with the exclusion of the first 3 (HR: 2.20, 95% CI: 1.28-3.80) or 5 (HR: 2.05, 95% CI: 1.08-3.89) years of observation showed consistent findings.

Conclusion:
AD may be an independent risk factor for new-onset dementia. Clinicians may monitor the trajectory of neurocognitive function among elderly patients with AD. Additional studies elucidating the pathomechanisms between AD and subsequent dementia are warranted.

Annotation

The finding:
Atopic dermatitis (AD) has previously been associated with higher rates of inflammation-mediated disorders such as diabetes, hypertension, and cerebrovascular diseases. These disorders are also considered to be risk factors for dementia. However, the direct relationship between AD and dementia has not been previously investigated. In this longitudinal cohort study, the investigators found a possible association between AD and the subsequent development of dementia, as compared to a cohort of matched control subjects.

Strength and weaknesses:
Strengths include the size of the study as well as a matched control group and longitudinal data. However, limitations relate to the database itself, as it did not include data prior to 1996 and thus no information regarding diagnosis of AD before this date was available. The authors pointed out that some of these subjects may have remitted AD and may have been erroneously included in the control group. In addition, the study analyses did not account for the use of antihistamine drugs, which are commonly used in AD and have also been found to have an association with a later diagnosis of dementia.

Relevance:
Knowledge of this potential association between AD and later development of dementia may guide C-L psychiatrists in developing treatment plans for patients who suffer from this skin condition.

Type of study:
Cohort study

Also of interest – PUBLICATION #4 — Psychodermatology

Posttraumatic stress disorder and the associated risk of autoimmune skin diseases: A nationwide population-based cohort study

Ying-Xiu Dai, Ying-Hsuan Tai, Yun-Ting Chang, Tzeng-Ji Chen, Mu-Hong Chen

Abstract: Psychosom Med. 2021 Apr 1;83(3):212-217. doi: 10.1097/PSY.0000000000000920.

Objective:
osttraumatic stress disorder (PTSD) is known as a risk factor for various immune-related disorders; however, the association between PTSD and related autoimmune skin diseases (ASDs) remains unclear. This study aimed to investigate the association of PTSD with the risk of related ASDs.

Methods:
Participants were recruited from the National Health Insurance Research Database in Taiwan. We included 9801 patients with PTSD and 39 204 matched controls to assess the risk of developing ASDs. Cox regression model was used for analyses.

Results:
After adjusting for confounders, we found an increased risk of ASDs among the patients with PTSD (adjusted hazard ratio [aHR], 3.00; 95% confidence interval [CI], 2.21-4.07) compared to that among matched controls. Statistically significant associations were found between PTSD and 5 individual ASDs, including psoriasis (aHR, 3.81; 95% CI, 1.90-7.67), lichen planus (aHR, 31.63; 95% CI, 4.00-249.91), alopecia areata (aHR, 4.77; 95% CI, 2.47-9.20), autoimmune bullous diseases (aHR, 9.55; 95% CI, 1.98-45.99), and vitiligo (aHR, 16.06; 95% CI, 4.48-57.54).

Conclusions:
Patients with PTSD had an increased risk of developing ASDs compared to the matched controls. Further studies are needed for better understanding of the underlying mechanisms.

Annotation

Annotation (unstructured)The study authors posited a correlation between PTSD and the subsequent development of an autoimmune skin disease (ASD), mediated by the common denominator of inflammation. Based on previous studies, PTSD has been found to cause alterations in the immune system, mediated by stress. Similarly, ASDs can also be caused and exacerbated by stress. This study, using the National Health Insurance Research Database (NHIRD) in Taiwan, recruited subjects with a diagnosis of PTSD and randomly selected matched controls without PTSD and then followed them until theu received a diagnosis of ASD, the end date of study period, or withdrawal from the NHIRD. The investigators found a 3-fold higher risk of certain ASDs in the PTSD cohort compared to the control group, though not for all ASDs considered.

Type of study (EBM guide):
Cohort study