Drug-Induced Psoriasis

Section 8.6 briefly lists medications that can trigger psoriasis, but the topic deserves its own chapter given the expanding pharmacopoeia and the rising use of immune-modulating drugs in oncology, rheumatology, and gastroenterology. Drug-induced psoriasis can present as de novo disease (new onset in a patient without prior psoriasis), exacerbation of pre-existing disease, or paradoxical psoriasis (new psoriasis caused by a drug that is itself used to treat psoriasis).

9.1 Classical Drug Triggers

The following medications have well-established associations with psoriasis onset or exacerbation, supported by decades of clinical observation:

Beta-blockers (propranolol, atenolol, metoprolol) are among the most frequently implicated. The mechanism involves blockade of b2-adrenergic receptors on keratinocytes, which normally promote cyclic AMP production and inhibit proliferation. Beta-blockade removes this brake, promoting keratinocyte hyperproliferation and reducing intracellular calcium levels in ways that mimic the psoriatic phenotype (Kim & Del Rosso, 2010).

Lithium, used for bipolar disorder, triggers or worsens psoriasis in approximately 45% of psoriasis patients who take it. Lithium inhibits inositol monophosphatase and glycogen synthase kinase-3b (GSK-3b), leading to increased pro-inflammatory cytokine production and impaired keratinocyte differentiation (Balak & Hajdarbegovic, 2017).

Antimalarials (chloroquine, hydroxychloroquine) exacerbate psoriasis in 18-42% of patients. The mechanism is thought to involve inhibition of transglutaminase activity, which is essential for normal epidermal differentiation, and disruption of intracellular antigen processing (Balak & Hajdarbegovic, 2017). This matters because hydroxychloroquine is widely prescribed for rheumatologic conditions that may co-exist with psoriasis.

Interferons (IFN-a, IFN-b) directly activate the psoriatic cascade by stimulating plasmacytoid dendritic cells and promoting Th1/Th17 differentiation, essentially amplifying the same initiation pathway described in Section 6.2 (Griffiths et al., 2021).

Terbinafine, an antifungal agent, has been associated with new-onset and exacerbated psoriasis, including generalised pustular forms. The mechanism is poorly understood but may involve modulation of cytokine profiles.

Research stage: Established. Evidence strength: High. Supported by decades of case series, systematic reviews, and pharmacovigilance data.

9.2 Immune Checkpoint Inhibitors

The growth of cancer immunotherapy has introduced a new category of drug-induced psoriasis. Immune checkpoint inhibitors (ICIs), including anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), and anti-CTLA-4 (ipilimumab) agents, work by removing the brakes on anti-tumour immunity. The trade-off: they can also unleash autoimmune responses against healthy tissues.

Psoriasis or psoriasiform dermatitis occurs in approximately 2-5% of ICI-treated patients. Presentations include exacerbation of pre-existing plaque psoriasis, de novo plaque psoriasis, guttate psoriasis, and, less commonly, pustular or erythrodermic forms (Balak & Hajdarbegovic, 2017). The onset typically occurs 2-16 weeks after treatment initiation.

Management requires careful balancing of dermatological and oncological needs. Mild cases may be managed with topical corticosteroids alone. Moderate-to-severe cases may require apremilast, which targets PDE4 rather than broad immune suppression and is being studied specifically for ICI-associated psoriasis. Acitretin is another option, as it acts on keratinocyte differentiation rather than immune suppression. Methotrexate and biologics may be used in refractory cases but require close oncological consultation, as systemic immunosuppression could theoretically diminish anti-tumour responses.

Research stage: Established. Evidence strength: Moderate-High. Growing case series and retrospective cohort studies; specific management guidelines published by ESMO and NCCN.

9.3 Biologic Paradoxical Reactions

One of the more counterintuitive phenomena in dermatology is paradoxical psoriasis: the development of new psoriatic lesions, or a morphological switch (e.g., plaque to pustular), in patients receiving biologic therapy for psoriasis or other inflammatory conditions. This occurs most frequently with TNF-a inhibitors (infliximab, adalimumab, etanercept) at rates of approximately 2-5%, but has also been reported with vedolizumab (anti-integrin, used for IBD) and rituximab (anti-CD20, used for lymphoma and rheumatoid arthritis) (Balak & Hajdarbegovic, 2017).

The proposed mechanism involves a cytokine imbalance: TNF-a blockade upregulates IFN-a production by plasmacytoid dendritic cells (the same type I interferon pathway implicated in psoriasis initiation, Section 6.2), which can paradoxically trigger a psoriatic cascade in genetically predisposed individuals.

Management typically involves switching to a biologic with a different mechanism of action, for example, from a TNF-a inhibitor to an IL-17 or IL-23 inhibitor. In mild cases, topical therapy may be sufficient without discontinuing the offending biologic.

Research stage: Established. Evidence strength: Moderate. Registry data (BADBIR, PSOLAR), systematic reviews, and case series.

9.4 Other Drug Triggers

Several additional medication classes have been associated with psoriasis exacerbation, typically supported by case reports or small case series rather than large epidemiological studies:

Dupilumab (an anti-IL-4/IL-13 biologic used for atopic dermatitis, asthma, and chronic rhinosinusitis) has emerged as a notable trigger of de novo psoriasis and psoriasiform dermatitis. A systematic review identified over 100 published cases, with onset typically 4-16 weeks after initiation (Gori et al., 2022). The proposed mechanism involves a Th2/Th17 imbalance: by potently suppressing the Th2 axis (IL-4, IL-13), dupilumab may remove a counterbalancing brake on the Th17 pathway that drives psoriasis. This is clinically important because atopic dermatitis and psoriasis were traditionally considered opposite poles of the immune spectrum (Th2 vs Th17), and dupilumab can apparently push patients from one pole to the other. Most cases resolve with topical treatment or switching to a different atopic dermatitis therapy, though some patients develop persistent plaque psoriasis.

• ACE inhibitors and angiotensin receptor blockers (sartans): May modulate inflammatory pathways through bradykinin accumulation and angiotensin II effects on T-cell function.
• NSAIDs (particularly indomethacin): May disrupt the balance between pro-inflammatory and anti-inflammatory prostaglandins.
• VEGF/tyrosine kinase inhibitors (sorafenib, sunitinib): Used in oncology; may trigger psoriasis through paradoxical immune activation.
• Antibiotics (tetracyclines, penicillins): Sporadic reports, mechanism unclear; may relate to microbiome disruption.
• Imiquimod: A TLR7 agonist used for actinic keratoses and basal cell carcinoma; directly activates the same innate immune pathway (TLR7 to IFN-a) that initiates psoriasis (Section 6.2).

Research stage: Established. Evidence strength: Low-Moderate. Primarily case reports and small case series; mechanisms plausible but not definitively proven.

9.5 Rapid Corticosteroid Withdrawal and Rebound

Systemic corticosteroids are generally avoided in psoriasis because, while they can produce rapid improvement, their withdrawal frequently triggers severe rebound flares, including conversion from stable plaque psoriasis to pustular or erythrodermic forms. These can be life-threatening. The mechanism involves corticosteroid-induced suppression of the HPA axis and IL-2 production; upon withdrawal, a compensatory surge in pro-inflammatory cytokine production overwhelms the skin’s capacity to maintain homeostasis (Griffiths et al., 2021).

This phenomenon also occurs with potent topical corticosteroids applied to large body surface areas, particularly when stopped abruptly rather than tapered. Best practice involves gradual dose reduction (tapering) and transition to steroid-sparing agents (Section 23).

Research stage: Established. Evidence strength: High. Well-characterised over decades of clinical practice; reflected in all major clinical guidelines.

9.6 Management Principles

When drug-induced psoriasis is suspected, the following framework guides clinical management:

1. Identification: Maintain a high index of suspicion. The temporal relationship between drug initiation and psoriasis onset/exacerbation is the primary diagnostic clue. The Naranjo adverse drug reaction probability scale can help assess causality.
2. Causality assessment: Consider whether the implicated drug is a known trigger, whether the timeline is consistent, and whether alternative explanations (natural disease progression, a new environmental trigger) are plausible.
3. Risk-benefit analysis: Not all drug-induced psoriasis requires discontinuation. If the offending drug is essential (e.g., lithium for bipolar disorder, ICI for cancer), psoriasis may be managed with concurrent topical or systemic therapy.
4. Switching strategies: When discontinuation is appropriate, substitute medications within the same class that lack psoriasis-triggering properties. For example, calcium channel blockers may replace beta-blockers; valproate or lamotrigine may replace lithium.
5. Monitoring: After discontinuation, improvement typically occurs within weeks to months, though some patients develop persistent psoriasis that outlasts the drug exposure.

Research stage: Established. Evidence strength: Moderate. Based on expert consensus, clinical guidelines, and case series rather than randomised trials of management strategies.