Atopic dermatitis patients experience broad range of comorbid conditions
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Key takeaways:
- Among patients with atopic dermatitis, 40.5% also have rhinitis, 25.7% also have asthma and 14.2% also have both.
- Children and adults with atopic dermatitis are at increased risk for depression.
Atopic dermatitis is associated with atopic and nonatopic comorbidities as well as ocular, psychiatric, infectious, endocrine, autoimmune and cardiovascular diseases, in addition to some cancers, according to a review.
Clinicians should consider these comorbidities when prescribing treatment for patients with AD, Jacob P. Thyssen, MD, PhD, DMSc, chief consultant, department of dermatology, Bispebjerg Hospital, and colleagues said in the review of more than 120 studies, published in The Journal of Allergy and Clinical Immunology.
“We have over the years in the group of Danes and Americans made numerous systematic review articles and meta-analyses of a very high quality to examine the association of AD and nearly all comorbidities you can think of that may be common or severe,” Thyssen told Healio.
Atopic and nonatopic comorbidities
Among patients with AD overall, the researchers said, 40.5% also had rhinitis, 25.7% also had asthma, and 14.2% had both in addition to AD. Also, 28.6% of adults had food sensitivity and 24.1% had food allergy, with children experiencing even higher proportions.
The odds of having an atopic disease increased by a factor of three to four among patients with AD, the researchers said, partly due to shared genetics. When AD is more severe, risks for atopic comorbidities such as asthma increased as well, the researchers continued.
AD also was associated with the allergic and non-allergic forms of asthma and rhinitis, the researchers said, adding that nasal polyposis and eosinophilic esophagitis were more common among patients with AD too.
When considering treatment, the researchers advised clinicians to screen patients with AD for gastrointestinal and respiratory atopic symptoms since they may impact treatment selection.
Ocular disease also was part of the AD syndrome, the researchers said, with conjunctivitis reported by 31.7% of patients with AD and 13.3% of control patients. The researchers characterized allergic conjunctivitis as most common and atopic keratoconjunctivitis and infectious conjunctivitis as much less common.
Also, 22% of patients with AD reported blepharitis, 9.1% reported dry eye disease and 1.4% reported keratitis. The researchers advised clinicians to ask patients with AD about ocular symptoms and perform clinical examinations when relevant as well.
Calling the impact of AD on mental health potentially substantial, the researchers reported significantly higher odds of AD with depression and anxiety in adults, in addition to higher odds for depression in children and suicidality in adults and adolescents.
Among adults with AD, 20.1% reported depression, 14.9% reported clinical depression, 29.3% reported antidepressant use and 12.2% reported suicidality, compared with 14.8% reporting depression, 12.6% reporting clinical depression, 20.3% reporting antidepressant use and 6.4% reporting suicidality among controls.
Depression rates among children included 29.3% of those with AD and 20.3% of those who did not have AD, with one study confirming the association between AD and psychiatric disease among children, the researchers said.
Topical, oral systemic and biologic treatments for AD improved depression and depressive symptoms, the researchers said, suggesting that these symptoms may be related to AD severity and modifiable with reduced AD severity.
Odds for alopecia areata increased by up to a factor of 10 for patients with AD in a bidirectional association, with risks increasing with each additional atopic condition a patient may have.
Vitiligo, chronic urticaria, celiac disease, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis were 1.5 times to twice as common among patients with AD, partly due to shared genetic risk variants, with elevated risks for autoimmune disease among patients with a history of smoking as well.
Specifically, 7.9% of adults and 2% of children with AD also had an autoimmune disease, compared with 5.7% of adults and 1% of children who did not have AD. Further, AD was associated with 18 of 32 autoimmune disorders in adults and 13 of 24 in children.
The researchers also found associations between AD and smoking, overweight and obesity in Asia and North America in addition to a positive association between AD and hypertension, particularly for patients with severe disease, with elevated risks for those patients who use cyclosporin.
Prolonged and intense use of topical corticosteroids partly explained an elevated risk for type 2 diabetes with AD, the researchers continued, along with very modestly elevated risk for various cardiovascular disease (CVD) outcomes. When relevant, the researchers recommended, specialists may diagnose and address CVD risk factors.
As AD leads to impaired cellular immunity, the researchers said, risks for viral skin infection increased with AD. Associations included herpes simplex, varicella zoster, verrucae and molluscum contagiosum, with a slightly increased risk for SARS-CoV-2 infections.
AD also increased the risk for Staphylococcus aureus colonization by a factor of 20 with a severity-dependent association, the researchers said, along with an association with methicillin-resistant Staphylococcal infection.
The researchers additionally found 1.3-fold to twofold increased risks for ear infection, strep throat, and urinary tract infection with AD, plus increased risks for upper and lower respiratory tract infections and a 1.5-fold increased risk for tuberculosis.
Point prevalence of hand eczema increased by a factor of two and lifetime prevalence increased by a factor of four, with similar elevations in risks for occupational hand eczema.
Also, the risk for allergic contact dermatitis increased by a factor of 1.5 for patients in general population studies with milder forms of AD. Clinical populations including patients who typically are seen in hospitals with more severe AD, however, experienced significantly lower risks for allergic contact dermatitis.
Additional factors
Tobacco smoking, physical inactivity, vitamin D deficiency, corticosteroid and psycholeptic use, and other risk factors for osteoporosis were associated with AD as well, the researchers said, indicating that patients with AD indirectly may be at increased risk for osteoporosis and major osteoporotic fractures.
In fact, the researchers said, the American Academy of Dermatology has recognized an association between AD in adults and osteoporosis, with high-quality evidence, and bone fractures, with evidence of moderate quality.
The researchers further found that risk for keratinocyte cancer increased by a factor of approximately 1.3 to 1.5 among patients with AD, but there was no association between AD and pancreatic cancer.
Lower levels of filaggrin and the degradation product urocanic acid, which is an important photoreceptor, may elevate risks for skin cancer, the researchers continued. Elevated risks for actinic keratosis and keratinocyte cancers were found as well, with higher risks for patients with homozygous filaggrin gene mutations.
Adult patients with AD who smoked had a higher Charlson comorbidity index (CCI) than controls in a Danish study, while adult patients with psoriasis and adult patients with AD had similar CCI scores in a U.S. study.
Compared with controls, patients with AD had slightly increased rates of all-cause mortality due to CVD, infections and urogenital diseases in studies from Denmark. A registry in the United Kingdom, meanwhile, found a severity-dependent association in increased all-cause mortality risk, primarily due to infectious, digestive and genitourinary diseases.
Conclusions
The results were not surprising for the authors.
“Since we already knew the results from many years of work, I will say [there were] no new insights for the authors. But, having the nice overview of all studies, we can now confirm the magnitude of associations and compare them,” Thyssen said.
“We see that allergic diseases, mental health problems and infections very frequently occur in AD patients, whereas autoimmune disease and major adverse cardiovascular events also are associated but generally are less common in absolute numbers,” he continued.
Due to these associations, the researchers suggested that Janus kinase (JAK) inhibitors and biologics approved for irritable bowel disease, rheumatoid arthritis, alopecia areata and severe asthma may be preferable for selected patients with comorbid autoimmune disease.
But due to an association between JAK inhibitor use and increased risk for cancers, Thyssen said, clinicians should prioritize other treatments in patients with these risk factors. Also, he said, JAKs may increase infections, which are more common with AD too.
Since allergic disorders are more common, Thyssen continued, biologics are worth considering since they reduce the severity of these disorders. However, biologics may improve or worsen conjunctivitis, which is more common with AD as well.
Overall, the researchers concluded, clinicians should be aware of these associations and their impacts on AD as well as how they may affect treatment. Meanwhile, Thyssen said that he and his colleagues will study the severity of these comorbid conditions.
For more information:
Jacob P. Thyssen, MD, PhD, DMSc, can be reached at jacob.pontoppidan.thyssen@regionh.dk.
Perspective
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This paper is very important, as it highlights that AD is associated with a number of other medical comorbidities. Although many of these associations have been known for some time, this study does an excellent job of clearly outlining what the current evidence shows as well as recent additions to our understanding of diseases associated with AD. One key takeaway for doctors is that considering comorbidities when assessing patients and selecting treatment approaches is extremely important. Next steps in this research may be to further assess the associations identified, as well as to evaluate outcomes when considering comorbidities with treatment plans.
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