What Everyone with Psoriasis Needs to Know About PDE4 Inhibitors
Psoriatic Arthritis (PW) is a chronic inflammatory skin disease characterized by psoriasis, hyperkeratosis congenita, and/or atopic dermatitis. PW affects approximately 1% of the population worldwide. Although there are no specific treatments for PW, it is curable if diagnosed early enough.
Psoriasis is a genetic disorder caused by an imbalance between the immune system’s T cells and its natural killer (NK) cells. A person’s own NK cell number determines whether they will develop psoriasis or not. Approximately 30%-50% of Caucasians carry one copy of the APC gene, while only 10%-20% of Asians have this allele.
If a person with one or two copies of the APC gene develops psoriasis, it is likely that they have a greater number of T cells, which attack their skin cells. The higher number of T cells results in increased insulin resistance, as the body is trying to create more leptin to control the leptin-resistant immune T cells.
The degree of psoriasis does not change the risk or likelihood of developing psoriatic arthritis. In fact, 15%-20% of people with psoriasis develop some form of arthritis, most commonly in the form of ankylosing spondylitis. There is a higher risk of other autoimmune disorders, such as Crohn’s disease, ulcerative colitis, and celiac disease.
Although diet does not cause psoriasis, it can make it worse and a proper diet can improve the condition. Anti-inflammatory diet guidelines recommend eliminating most red meat and avoiding processed foods.
The PDE4 enzyme breaks down cyclic guanosine monophosphate (cGMP) in the body. By inhibiting the PDE4 enzyme, it is possible to raise cGMP levels, which should improve psoriasis symptoms as well as lower blood pressure. Cyclic guanosine monophosphate is involved in a variety of processes in the body, including vascular permeability and smooth muscle relaxation.
PDE4 inhibitors are used to treat several medical conditions, especially psychiatric ones such as anxiety and depression. The effectiveness of these drugs at treating psoriasis is still being researched.
Theophylline is an alkaloid drug used to treat asthma and bronchial issues. It is a non-selective phosphodiesterase (PDE) inhibitor.
PDE1, PDE2, and PDE3 are all high in psoriatic lesions. This indicates that these particular enzymes may be contributing to the inflammation seen in these diseases, which is why selective inhibitors of these three enzymes are beneficial. PDE4 is an exception, as it does not seem to be present in psoriatic lesions.
Frequently used tetracyclines, such as doxycycline and minocycline, are commonly used to treat severe and moderate plaque psoriasis. Typically, these are given in higher dosages than when treating an infection, and should only be taken under the care of a physician. Improvement is usually seen in 2-3 weeks, with a maximum benefit at around 4 weeks.
Treatment is usually given for 3-6 months and is then discontinued if the patient’s condition has improved, although some patients can remain on a lower dosage for prolonged periods of time. Doxycycline is better tolerated in the stomach than minocycline.
The mechanism of action of this drug class in treating psoriasis is not known. It is thought that the drugs may affect the way that T cells mature and interact with other cells.
Common Side Effects
Dehydration (from diarrhea)
Occasional Side Effects
Blistering skin lesions (with long-term use)
Diarrhea or loose stools (with long-term use)
Heartburn and indigestion (with long-term use)
Itching of skin (with long-term use)
Rash (with long-term use)
Serious Side Effects
Decreased white blood cell count
Severe muscle weakness
Tenesmus (with long-term use)
Tinnitus (ringing of the ears) (with long-term use)
Unusual bruising or bleeding (with long-term use)
Interactions with Other Drugs: Alcohol: Occasional alcohol consumption should not be reduced. However, regular excessive alcohol use (i.e., daily drinking) should be stopped due to the risk of liver damage.
Never drink alcohol while taking tetracycline antibiotics. If you do, you risk damaging your liver and may not be able to feel it happening. Antacids: The antacid drugs aluminum hydroxide, magnesium hydroxide, and calcium carbonate reduce the absorption of doxycycline in the stomach and should not be taken with this drug. Antibiotics: Erythromycin, and related drugs called the macrolides, are not recommended for use with tetracyclines as they reduce the absorption of tetracyclines in the body. Anticoagulants: Tetracycline may increase the effects of warfarin by reducing its breakdown in the liver. As a result, your blood won’t clot as easily and you may experience increased bleeding.
Sources & references used in this article:
Genomics and personalized medicine: what everyone needs to know by M Snyder – 2016 – books.google.com
Group for research and assessment of psoriasis and psoriatic arthritis 2015 treatment recommendations for psoriatic arthritis by LC Coates, A Kavanaugh, PJ Mease… – Arthritis & …, 2016 – Wiley Online Library
Treatment of irritant and allergic contact dermatitis by DE Cohen, N Heidary – Dermatologic Therapy, 2004 – Wiley Online Library
IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis by TW Kragstrup, M Adams, S Lomholt… – Therapeutic …, 2019 – journals.sagepub.com