Psoriatic arthritis can manifest itself in different domains. In addition to inflammation of the peripheral or axial joints, inflammation can also occur in the fingers (dactylitis), tendon attachments (enthesitis), skin and nails (psoriasis). Dr. Hok Bing Thio, dermatologist at Erasmus MC, treats a case of psoriatic arthritis in which complaints of the nails are in the foreground.
Case description
The case study concerns a 51-year-old woman who was referred by a fellow dermatologist for nail psoriasis. She particularly suffers from distal onycholysis (nail detachment) and pain complaints as a result. In addition, she has skin abnormalities on the tips of the fingers and on the heels. In the past she also suffered from joint problems in the fingers and wrists. At the moment it is quiet.
The manifestations of psoriatic arthritis in the woman in the case: distal onchyolysis, skin lesions on the fingertips and on the heels.
In addition to the psoriatic arthritis, the lady suffers from hypothyroidism for which she takes levothyroxine (125 mcg). She also had a gastric bypass. Finally, she suffers from hay fever and allergic conjunctivitis. There is no family history of psoriasis or atopy.
The woman herself rates her complaints as moderately severe (Numeric Rating Scale (NRS) of 6 on a scale of 0-10). She works as a coach for young people with an intellectual disability. In connection with the visibility of the nail abnormalities, she would like a treatment that removes the complaints.
What treatments has the patient already had?
“Elsewhere, the lady has already been treated with local therapy (mometasone ointment). At the time of referral she uses calcipotriol/betamethasone foam, cooling ointment without rose oil and if necessary calcitriol for fissures (under occlusion, 1x/week). To date, the local treatment unfortunately gives insufficient results. The lady does not want to use local corticosteroid injections. Partly at the request of the lady, she is referred to a tertiary center for systemic therapy.”
What is the underlying problem in nail psoriasis?
“The underlying problem in (nail) psoriasis is an immunological process characterized by an abnormal response of T helper (Th) cells. This not only involves Th1 cells, but also Th17 and Th22 cells. These last 2 cell types were only discovered at the beginning of the 21st century.1,2 These different types of T cells produce the following cytokines, among others: TNF-α (Th1 cells), IL-17 (Th17 cells), and IL-22 (Th22 cells). Under the influence of this, an inflammatory reaction can occur in the skin, nails and joints.”3
What form of systemic therapy is appropriate for this patient?
“Due to the underlying process, the patient was initially treated with immunosuppressive therapy with methotrexate (starting dose of 15 mg/week for 3 months). This had insufficient effect.”
“Following this, there were several options for further treatment. The first option is to increase the dose of methotrexate to 25 mg/week. This was not chosen because of the speed of the effect of treatment. It would be less motivating for the patient to continue on the chosen path after 3 months of treatment with methotrexate without this having any effect.”
“An alternative is the use of biologicals. These can be used for nail psoriasis in case at least 3 nails are involved and there are also skin problems and a reduced quality of life.4 In that case, the choice consists of TNF-α inhibitors, IL-17 inhibitors and IL-23 inhibitors. These biologicals inhibit the cytokines produced by Th1 cells (TNF-α) and Th17 cells (IL-17) and the stimulation of Th17 cells by IL-23.
“All 3 types of biologicals are basically effective for nail psoriasis. There is no explicit reason why one should try one or the other first. In the case of the current patient, we chose to directly block the effector cytokine IL-17 with an IL-17 inhibitor.”
“Treatment with the IL-17 inhibitor proved successful. Both the nail psoriasis and the skin abnormalities settled down. The patient has been referred back to the referring dermatologist.”
What are possible side effects of the chosen therapy?
“IL-17 plays an important role in the defense against extracellular bacteria, fungi and yeasts. Common side effects of the medication are upper respiratory infections. This side effect also applies to TNF-α and IL-23 inhibitors.5 In the case of IL-17 inhibitors, candida infection also occurs as a side effect.”6
Are there other factors to consider?
“In addition to the nail psoriasis, this patient also suffers from atopic complaints, namely hay fever and allergic conjunctivitis. Where nail psoriasis is mainly controlled by Th1 and Th17 cells, atopic reactions are mainly controlled by Th2 cells.
If Th1-/Th17- and Th2-mediated immune diseases occur in one patient, they can have a dampening effect on each other. Proper treatment of the nail psoriasis, in which the Th1/Th17 response is inhibited, can then lead to the patient suffering more from the atopic complaints. Fortunately, this was not the case in this patient’s case.”
Key messages
In nail psoriasis involving at least 3 nails, good effects can be achieved with biologicals such as TNF-α inhibitors, IL-17 inhibitors and IL-23 inhibitors.
If you suppress the Th1/Th17 response using biologics, there is a chance that Th2-mediated conditions such as atopy will flare up more. This also applies the other way around.
Common side effects when using biologics are upper respiratory tract infections. Candida infection can also occur as a side effect of IL-17 inhibitors.
References
- Annunziato F, Romagnani S. Arthritis Res Ther. 2009;11(6):257. Heterogeneity of human effector CD4+ T cells.
- Veldhoen M. The role of T helper subsets in autoimmunity and allergy Curr Opin Immunol. 2009;21(6):606-11.
- Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130(5):1373-83.
- Hadeler E, Mosca M, Hong J, Brownstone N, Bhutani T, Liao W. Nail psoriasis: a review of effective therapies and recommendations for management. Dermatol Ther (Heidelb). 2021;11(3):799-831.
- Pharmacotherapeutic Compass. Available via www.farmacotherapeutischkompas.nl. Accessed 28-Oct-2022.
- Davidson L, Van den Reek JMPA, Bruno M, et al. Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources. Lancet Reg Health Eur. 2021;13:100266.
