Lung disease and psoriasis
One of the significant symptoms of Covid-19 is a persistent cough and, in severe cases, shortness of breath. Whilst this is not the place to discuss the specific features or details of coronavirus infection, it’s a useful moment to review the various lung conditions associated with psoriasis and whether any of the current systemic drug treatments, may themselves be associated with respiratory symptoms such as cough and breathlessness.
Psoriasis and psoriatic arthritis are chronic, autoimmune disorders in which an inflammatory response is directed towards the body’s own tissue – specifically the skin and joints. Nowadays, it is well recognised that psoriasis is a systemic disease which may be associated with a variety of other disorders such as obesity, diabetes, cardiovascular disease (CVD) and inflammatory bowel disease.
Today there is emerging evidence to suggest that patients with psoriasis may also be more susceptible to a variety of respiratory (lung) diseases. Furthermore, some of the systemic drug treatments for moderate-severe psoriasis, may themselves have pulmonary side-effects, such as cough and breathlessness.
It is well known that psoriasis is a risk-factor for asthma. A recent meta-analysis of six studies, involving 66,772 cases of psoriasis and 577,415 controls showed that patients with psoriasis have a greater susceptibility to asthma1. The risk was greater in older patients (≥ 50 years) than in younger patients, though exactly why this should be the case is not clear.
The mechanism underlying the association between asthma and psoriasis is complex but is clearly related to the fundamental immunological mechanisms which the two conditions have in common.
Chronic Obstructive Pulmonary Disease (COPD)
COPD refers to a group of diseases that impair the flow of air to the lungs, making it more difficult to breathe. A recent (2015) systematic review and meta-analysis looked at the link between psoriasis and COPD2. The researchers concluded that people with psoriasis had an approximately two-fold greater risk of developing COPD, compared to the general population. The risk was higher in people with severe psoriasis. However, it should be noted that of the 44 initially eligible studies to be included in the analysis, only four were eventually included, two of which did not have information regarding smoking status.
A large study from Israel included 12,502 psoriasis cases matched with 24,287 controls and found the prevalence of COPD to be higher (5.7%) in psoriatic patients when compared with controls (3.7%). However, after taking into account other factors such as smoking, obesity, gender and socioeconomic status, the association was much less evident, though still statistically significant3.
A recent (2018) study from Denmark set out to measure lung function in patients with psoriasis. Hansen and colleagues studied 20,422 adults in the Danish General Suburban Population Study, which included 1,173 people with psoriasis and 19249 controls4. Participants carried out lung-function tests with hand-held spirometers, and answered various questions about whether they had psoriasis, shortness of breath and pneumonia during the past decade.
Results showed that patients with psoriasis exhibited a small reduction in lung function when compared with the controls, though after adjustment for smoking the differences were quite small (a point the authors concede). The authors speculate that patients with psoriasis may have sub-clinical airway inflammation and inflammatory pathways may coincide between psoriasis and inflammatory lung disease. It is important to note that no adjustment was made for obesity or physical activity in this study, both of which would be expected to have an effect.
Sarcoidosis, or sarcoid, is an uncommon disease in which certain inflammatory cells clump together and to form small lumps called granulomas. The organs most commonly involved are the lungs, skin and eyes. As a chronic inflammatory condition, sarcoid clearly has some features in common with psoriasis, and they may share common underlying mechanisms.
A large epidemiological study, essentially involving the whole of the Danish population (> 6 million subjects), has demonstrated a strong association between psoriasis and the risk of sarcoidosis5. Overall incidence rates were 1.18, 2.2 and 4.06 respectively, for patients in the control group and those with mild and severe psoriasis respectively. When the results were fully adjusted to take into account age and gender, the models showed that patients with mild psoriasis have about a 50% increased risk of developing sarcoidosis compared with the control group, whilst in those with severe psoriasis there is a 2.5-fold increase in risk. The association, such as it is, is almost certainly due to some overlap in the inflammatory and immunological pathways underlying both diseases.
However, it’s important to set this risk in context. Among the 70,125 who developed psoriasis over the study period, only 100 (0.14%) also developed sarcoidosis. In other words, in practice, the risk of any patient with psoriasis also developing sarcoid disease, is extremely small.
Interstitial Lung disease (ILD)
This is a technical term used to define an unusual and complex group of lung conditions – including interstitial pneumonia and pulmonary fibrosis – which have been observed in association with psoriasis. These conditions tend to cause progressive and irreversible scarring of lung tissue. In recent years, several publications have raised the question as to whether these conditions may be more common in patients with psoriasis.
In one study of 447 patients with advanced ILD, 21 (4.7%) were found to have concomitant psoriasis6. However, it is not obvious from this what the association between the two conditions is, or whether there is any true association. The prevalence of psoriasis in the general population in the UK is around 3%, so the finding of 4.7% prevalence in the ILD group, whilst significant, is not dramatically so. As the authors themselves concede, there is no obvious mechanism linking the two conditions and – it follows from this – that there may be no mechanism linking them.
Another study found interstitial pneumonia in 8 out of 392 (2%) of patients with psoriasis who were being treated with biologic agents for severe disease7. The average age of the patients was 73.5 years and they all had very mild (or no) symptoms. The authors speculate that there may be common mechanisms underlying psoriasis and interstitial pneumonia. They also concede that the population in their study was highly atypical: the incidence of pneumonia in a younger population with less severe psoriasis, would be much lower.
Studies show that individuals with psoriasis are more likely to be cigarette smokers, However, a recent (2016) study based on data from UK Health Improvement Network, suggests that patients with severe psoriasis may have an increased risk of lung cancer, independently of smoking status8. After adjusting for smoking and a range of other factors, those with severe psoriasis still had an approximately 60% greater risk of lung cancer when compared to patients with mild psoriasis. There was no association between psoriasis and risk of bowel, breast, prostate cancer or leukaemia.
It should be noted, however, that other studies have found no excess risk of lung cancer in psoriatic patients, once smoking status is taken into account. Whatever the truth of the matter, it’s clear that stopping smoking is the surest way for a patient with psoriasis to dramatically reduce the risk of lung cancer.
Symptoms of lung disease
All the conditions above may have different combinations of symptoms, but by far the most common are cough and breathlessness. Others include production of phlegm (sputum), wheezing and chest pain. If any of these become persistent, then you should seek medical advice.
Psoriasis medication and respiratory disease
Certain groups of drugs used to treat psoriasis, may themselves be associated with an increased risk of respiratory disease or symptoms.
Methotrexate, Ciclosporin and Acitretin are all systemic drugs used in the treatment of psoriasis. Whilst methotrexate has been reported to cause lung damage9, this is an exceedingly rare complication, so that all three can be regarded as generally safe from a respiratory viewpoint.
Biologics are a group of bioengineered drugs which target specific parts of the immune system. They treat diseases such as psoriasis by modulating the activity of messengers called cytokines which are at the heart of the inflammatory response in psoriasis.
There are two main mechanisms of action: (1) some drugs block the action of tumour necrosis factor (Anti-TNF), whilst others (2) block the action of another group of inflammatory molecules called interleukins.
The National Institute of Health and Care Excellence (NICE) recommends the use of biologics in patients who have not responded to the standard systemic treatments such as methotrexate, ciclosporin and acitretin. Examples of biologics used in psoriasis include: Humira (adalimumab),Enbrel (etanercept), Stelara (ustekinumab), Cosentyx (secukinumab),Kyntheum (brodalumab), Taltz (ixekizumab), Tremfya (guselkumab), Cimzia (certolizumab pegol), Skyrizi (isankizumab), Ilumetri (tildrakizumab) and Remicade (Infliximab).
Because they are immunosuppressants, almost biologics carry an increased risk of upper respiratory tract infections, though this is not usually sufficient to discontinue use of the drug.
Some of these medications, especially Anti-TNF drugs such as adalimumab, infliximab and etanercept, have a cough as a side-effect and may also cause an inflammatory reaction in the lungs10. In addition, Stelara (ustekinumab) has recently been shown to be associated with a non-infectious form of pneumonia11. There is, incidentally, no evidence that biologics increase the risk of cancer12.
Psoriasis is a multi-system disease and may be associated with an increased risk of a wide variety of respiratory diseases. The problem is in deciding what the level of that additional risk actually is.
One difficulty is that many (if not the majority) of studies which address the association between psoriasis and lung disease, fail to take into account three key risk factors – obesity, smoking status and physical activity - all of which are associated with respiratory problems and all three of which are more common in patients with psoriasis. Failure to adjust for these factors, may result in an over-estimate of the risks for the lung diseases referred to above.
The fact is that breathlessness and cough in a patient with psoriasis is much more likely to be due to smoking, obesity or poor fitness levels (due to physical inactivity) than to complex lung disease. Conversely, encouraging patients to stop smoking, maintain a healthy weight and take regular aerobic exercise, is the surest way of reducing the risk of respiratory disease in patients with psoriasis.
Nevertheless, it would seem reasonable to suggest that patients with psoriasis are at an increased risk of lung disease, even after they have made better lifestyle choices, though the level of this excess risk may be quite small. Some conditions such as sarcoid, and ILD have an uncertain association with psoriasis. Biologic medications have an increased risk of respiratory infections and may also cause a cough as a side-effect.
Any patient with persistent respiratory symptoms, especially breathlessness and cough, should be investigated appropriately.
- Patients with psoriasis have an increased risk of a variety of respiratory diseases, including asthma, COPD, sarcoid and ILD
- Whilst these conditions are important, they are relatively uncommon and do not represent a major cause of illness in patients with psoriasis
- The two most common symptoms of respiratory disease are breathlessness and cough and, in the patient with psoriasis, these are more likely to be due to obesity, cigarette smoking or poor cardio-respiratory fitness levels, than to anything more serious.
- All patients with psoriasis should be encouraged to stop smoking, maintain a healthy weight and take regular exercise
- Systemic treatments used in psoriasis (methotrexate, ciclosporin and acitretin) are generally safe and rarely cause respiratory problems
- Biologic treatments, likewise, may cause mild upper respiratory symptoms and cough, but these rarely require discontinuation of treatment; the exception being ustekinumab, which may cause a severe non-infectious pneumonia.
- Anti-TNF drugs may cause inflammation of the lungs and also have a cough as a recognised side-effect.
- Any patient with psoriasis and persistent respiratory symptoms – such as breathlessness and cough – should be referred for specialist investigation and treatment.
- Wang J, Ke R, Shi W, Association between psoriasis and asthma risk: A meta-analysis. Allergy Asthma Proc 2018; 39:103–109
- Li X, Kong L, Li F, Chen C et al. Association between Psoriasis and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis. 2015; PLoSONE 10(12): e0145221.doi:10.1371/journal.pone.0145221
- Dreiher J, Weitzman D, Shapiro J et al. Psoriasis and Chronic Obstructive Pulmonary Disease: A Case-Control Study. Br J Dermatol 2008; 159: 956-60.
- Hansen, P. R., Isaksen, J. L., Jemec, G. B., Kanters, J. K. and Ellervik, C. Pulmonary function in subjects with psoriasis: A cross‐sectional population study. Br J Dermatol 2018. Accepted Author Manuscript. doi:10.1111/bjd.16539
- Khalid U, Gislason GH, Hansen PR. Sarcoidosis in Patients with Psoriasis: A Population-Based Cohort Study. PLoS ONE 2014; 9(10): e109632. doi:10.1371/ journal.pone.0109632
- Ishikawa G, Dua S, Mathur A et al, Concomitant Interstitial Lung Disease with Psoriasis. Canadian Respiratory Journal Volume 2019, Article ID 5919304,
- Kawamoto H, Hara H, Minagawa S, et al. Interstitial Pneumonia in Psoriasis. Mayo Clin Proc Innov Qual Outcomes. 2018; 20;2(4):370-377
- Chiesa Fuxench ZC, Shin DB, Beatty AO, Gelfand JM. The Risk of Cancer in Patients with Psoriasis: A Population-Based Cohort Study in the Health Improvement Network. JAMA Dermatol 2016; 52: 282–290.
- Jakubovic, BD, Donovan A, Webster PM, Shear NH. Methotrexate-induced pulmonary toxicity. Can Respir J. 2013; 20: 153–155
- Thavarajah K, Wu P, Rhew EJ et al. Pulmonary Complications of Tumor Necrosis Factor Targeted Therapy. Respir Med. 2009; 103: 661–669
- Brinker A, Cheng C, Chan V. Association of Non-infectious Pneumonia with Ustekinumab Use JAMA Dermatol 2019;155:221-224.
- Kimball AB. Abstract 102. American Academy of Dermatology Summer 2014; Chicago; Aug. 6-10, 2014.
Dr David Ashton MD PhD