Research provides evidence of the efficacy and safety of a treatment for nail psoriasis (when the nails are affected by the disease). Researchers from the Graduate Program in Pharmacology and the Dermatology Division of the Department of Internal Medicine at Unicamp investigated the use of low-dose methotrexate administered through a single injection around the nails. The results indicate improvement of the disease for months, with a possible reduction in the toxicity associated with the medication.
Psoriasis: far beyond aesthetics
Psoriasis is estimated to affect 2% to 5% of the world’s population. It can cause different symptoms, such as plaque-like skin lesions, joint pain and stiffness, and even abnormal nail growth and discoloration. Although it is not a contagious disease, misinformation still causes significant social stigma, leading to isolation of people with psoriasis. This deeply affects patients’ self-esteem and quality of life and may lead to depression and anxiety.
Psoriasis is an autoimmune disease, meaning the body learns to attack itself. Healthy cells are mistaken for threats and become targets of the immune system. It is like an army that, instead of attacking the enemy, becomes confused and turns against the very population it was meant to defend. The cells under attack are those of the skin, joints, and nails. The immune response produces inflammation to destroy the supposed enemy, causing pain, swelling, redness, burning, itching, and lesions.
The inflammation caused by psoriasis is not limited to the affected cells; it impacts the entire body. Because it is chronic (long-lasting), it can evolve into a systemic condition (affecting the whole organism). Consequently, patients may develop complications such as cardiovascular diseases, metabolic disorders (diabetes, obesity, high cholesterol, etc.), and even an increased risk of certain types of cancer.
The disease is multifactorial, meaning several factors contribute to its development. These include genetic predisposition, stress, alcohol consumption, smoking, and certain medications such as chloroquine and lithium. It usually manifests between the ages of 18 and 39, affecting men and women equally. Psoriasis has no cure, but it can be controlled with medication. In addition, cognitive behavioral therapy is recommended to help patients cope with the psychological impacts of the disease.
Nail psoriasis: when the disease affects the nails
Nail psoriasis is the form of the disease that affects the nails. It occurs in association with other types of psoriasis, affecting more than 50% of patients with plaque psoriasis (the most common form) and more than 80% of those with psoriatic arthritis (when the joints are involved).
Nail psoriasis can manifest in various ways. The nails may develop small pits, white spots, red patches, horizontal depressions (Beau’s lines), crumbling, discoloration, and separation from the nail bed. Bleeding beneath the nails and inflammation of the surrounding skin (psoriatic paronychia) may also occur. Patients often report pain, reduced tactile sensitivity, and difficulty performing daily activities such as holding objects or tying shoelaces.
Why Is nail psoriasis so challenging to treat?
Currently, the treatment of nail psoriasis faces several challenges. Many treatments show noticeable results only after one year. A widely used medication is methotrexate, which is also employed in the treatment of several other autoimmune diseases. It is an immunosuppressant, meaning it reduces the activity of the immune system, which in autoimmune diseases is dysregulated and attacking the body itself. Returning to the army metaphor, methotrexate acts like a calming agent for this army, making it less aggressive toward its own population.
The problem is that methotrexate treatment may cause several side effects, including liver toxicity (hepatotoxicity), mouth ulcers (ulcerative stomatitis), nausea, and reduced immunity.
In severe cases of nail psoriasis, usually associated with psoriatic arthritis, oral methotrexate is recommended. In these cases, the toxic effects mentioned above are more frequent, since the medication taken orally is absorbed and distributed throughout the entire body. However, methotrexate is also highly effective in treating psoriatic arthritis. It is important to remember that psoriatic arthritis affects the joints and may lead to debilitating complications such as physical deformities and loss of mobility. Therefore, in methotrexate treatment, the benefits may outweigh the side effects.
In milder cases of nail psoriasis, when psoriatic arthritis is not present, local treatment or intralesional injections (beneath or around the nails) are recommended. The injections are usually not painful because they are administered under anesthesia. This type of treatment tends to be less effective but also presents lower toxicity. There is still limited research on these approaches to better define their efficacy and safety.
The research
For this reason, Prof. Dr. Gilberto De Nucci, from the Graduate Program in Pharmacology, and Prof. Dr. Renata Ferreira Magalhães, from the Dermatology Division of the Department of Internal Medicine, decided to investigate treatment with low-dose periungual (around the nail) methotrexate injections. The study was published in the Journal of the American Academy of Dermatology and is available online. The project also involved other researchers from Unicamp’s Graduate Program in Pharmacology: in addition to Prof. Gilberto, Dr. Luiz Fernando Ribeiro and alumna M.Sc. Tainah Babadopulos Magalhães. The research was funded by São Paulo Research Foundation (Grant numbers 23/15165-7 and 23/01267-2).
The aim of the study was to characterize the pharmacokinetics of the treatment, that is, the route methotrexate takes in the body, from injection and entry into the bloodstream to its excretion (mainly in the urine). Five patients received periungual injections of 20 mg of methotrexate (divided among the ten fingernails). At different time points, the drug concentration in plasma (the liquid portion of blood, excluding cells such as red and white blood cells) was measured.
Promising results
The findings reinforce the treatment’s effectiveness. There was approximately 60% remission of nail psoriasis after one to four months. It is believed that the success of this approach is due to the fact that periungual injection allows methotrexate to remain in the nail bed (the soft tissue beneath the nail) for much longer than with other routes of administration, such as oral or intravenous. Thus, the nail grows under continuous exposure to the medication.
Safety also appears to be greater with periungual injection compared to oral and intravenous routes. Twenty-four hours after administration, plasma methotrexate concentration was so low that it could not be detected. The plasma concentration considered critical for toxicity is 10 µg/mL after 24 hours. The results showed values well below this threshold, even at peak concentration: about 4.33 µg/mL approximately one hour after injection.
The nail bed is believed to act as a slow-release reservoir of the medication. In this way, most of the drug remains in contact with the nails for an extended period, while only small amounts slowly reach the bloodstream. It is like a bucket full of water with a small hole at the bottom: it will leak, but slowly; and the bucket will remain full for quite some time.
A step forward toward more personalized treatments
The relevance of the study was highlighted by the editor of the Journal of the American Academy of Dermatology, Prof. Dr. Dirk Michael Elston. In an editorial, he emphasized that, as a dermatologist, he already uses this treatment in patients without psoriatic arthritis. He mentioned that he usually combines periungual methotrexate injections with triamcinolone acetonide (a corticosteroid anti-inflammatory), in addition to topical treatment. He also noted that this is a cost-effective approach—that is, economical and with good results.
However, Prof. Dirk reinforces that further studies are still needed to confirm the treatment’s safety. In the publication, the authors themselves acknowledge limitations, such as the small number of patients and comparison with previous case reports rather than with a control group. Nevertheless, the importance of the publication in advancing the consolidation of safety for this type of approach is undeniable, as Prof. Dirk comments.
Nail psoriasis still imposes physical and emotional limitations on many patients. The results obtained offer an encouraging perspective. The study paves the way for a more targeted, effective, and potentially safer approach. Although larger studies are still needed, the research represents an important step toward more personalized treatments capable of alleviating both the visible symptoms of the disease and the invisible burden it places on quality of life.
To learn more:
Brazilian Society of Dermatology – Psoriasis
Psoriasis: Epidemiological and Pathophysiological Aspects – A Literature Review
Brazilian Association of Psoriasis, Psoriatic Arthritis and Other Chronic Skin Diseases
Nail Psoriasis: A Review of Treatment Options
Letter from the Editor: Topical and Intralesional Therapy for Nail Psoriasis
Written by:
Mia Schezaro Ramos
Pharmacist. Ph.D. in Pharmacology. Science journalist, illustrator, trans, Nintendo enthusiast, K-pop fan, and dependent on physical exercise to stay sane.