Paradoxical psoriasis is a unique skin condition that emerges in individuals being treated with specific biologic medications for other autoimmune disorders. The name highlights a contradiction: a drug designed to suppress an inflammatory disease inadvertently triggers a different inflammatory skin response. This reaction can manifest as the new onset of psoriasis in a patient with no prior history or as a significant worsening of pre-existing, but previously controlled, psoriasis. The condition presents a clinical puzzle, forcing physicians and patients to weigh the benefits of a successful therapy against an unexpected side effect.
The Underlying Cause and Associated Medications
Paradoxical psoriasis is most frequently linked to a class of biologic drugs known as tumor necrosis factor-alpha (TNF-α) inhibitors. These medications are highly effective treatments for a range of autoimmune diseases, including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and even classic psoriasis itself. Common examples of these drugs include infliximab, adalimumab, and etanercept. While these therapies work by blocking TNF-α, a protein that promotes inflammation, this action appears to disrupt the immune system’s equilibrium.
The exact mechanism is not fully understood, but a leading theory involves an alternative inflammatory pathway. By suppressing TNF-α, the body’s immune response may shift, leading to an overproduction of other signaling proteins called type I interferons. Plasmacytoid dendritic cells (pDCs) are recruited to the skin and produce large amounts of these interferons. This surge of interferon activity, without the typical T-cell activation seen in classic psoriasis, is thought to drive the development of the psoriasis-like skin lesions.
This reaction is not immediate, often developing months after starting the anti-TNF medication, with an average onset of around 11 months. Studies indicate that between 2% and 5% of patients using TNF-α inhibitors may develop this condition. Certain factors appear to increase this risk, including being female or a smoker.
Symptoms and Diagnosis
The clinical presentation of paradoxical psoriasis can be varied and mimic several forms of classic psoriasis. Patients may develop well-defined, red, scaly patches known as plaque-like psoriasis. Another common manifestation is pustular psoriasis, characterized by the appearance of small, pus-filled bumps, which frequently occur on the palms of the hands and soles of the feet (palmoplantar pustulosis). Scalp and flexural (skin folds) involvement are also regularly reported.
Diagnosing paradoxical psoriasis hinges on a careful evaluation of the patient’s clinical context. A dermatologist will conduct a thorough physical examination of the skin lesions and take a detailed medical history. The primary diagnostic clue is the patient’s current use of a biologic drug, like a TNF-α inhibitor, creating a temporal link between the medication and the skin eruption.
To confirm the diagnosis and exclude other potential skin diseases, a skin biopsy may be performed. In this procedure, a small sample of the affected skin is removed and examined under a microscope. While the histological findings can overlap with classic psoriasis, there are sometimes subtle differences that can help a pathologist confirm the paradoxical reaction.
Distinguishing from Classic Psoriasis
A primary distinction lies in their triggers. Paradoxical psoriasis is a drug-induced reaction to biologic therapies. In contrast, classic psoriasis is a T-cell mediated autoimmune disease resulting from a complex interaction between genetic and environmental factors, not a direct response to a specific medication.
The patient’s medical history provides another differentiator. Individuals with paradoxical psoriasis are being treated for another significant autoimmune condition, like inflammatory bowel disease or rheumatoid arthritis. Classic psoriasis can develop in otherwise healthy individuals.
While the appearance of the skin lesions can be similar, the immunological basis differs. Paradoxical psoriasis is driven by an innate immune response characterized by high levels of type I interferon, whereas classic psoriasis evolves into a T-cell autoimmune condition with memory T-cells that cause relapses. This lack of T-cell memory means that paradoxical psoriasis resolves without relapse once the offending drug is stopped.
Management and Treatment Strategies
Managing paradoxical psoriasis requires balancing the severity of the new skin condition against the effectiveness of the biologic drug for the patient’s primary disease. The decision is whether to continue or discontinue the causative medication. This choice is made on a case-by-case basis, based on how well the primary autoimmune disorder is controlled and how severe the psoriasis has become.
In cases where the psoriasis is mild and the patient’s primary disease is in remission, the decision may be to continue the biologic agent. The skin symptoms can be managed with topical treatments, such as prescribed corticosteroids or vitamin D analogues. For slightly more extensive cases, phototherapy (light therapy) may also be used to control the psoriasis while the patient remains on their medication.
If the psoriasis is severe, widespread, or unresponsive to topical therapies, discontinuing the offending drug is the most effective solution. This action frequently leads to the resolution of the psoriatic lesions. The patient is then transitioned to a different biologic medication that works through a different mechanism and is less likely to cause the same side effect, such as an IL-12/23 or IL-17 inhibitor.