‘Psoriasis Punctata’: An Under-Recognised Clinical Phenotype of TNF-Alpha Inhibitor-Induced Psoriasis

Abstract

Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat numerous inflammatory conditions. Paradoxical psoriasiform eruptions (‘TNF inhibitor-induced psoriasis’) are well-recognised adverse effects and can manifest as plaque, guttate, inverse, pustular, scalp psoriasis, as well as psoriasiform eruptions [1-3]. A small form of guttate psoriasis, termed here ‘psoriasis punctata’ has been seen routinely in our clinic. This morphology is underappreciated in literature. We aimed to characterise psoriasis punctata and compare its features with other subtypes of TNF-alpha-induced psoriasis.

Querying our institution's EMR system from 2004 to 2024, we identified 93 patients with TNF inhibitor-induced psoriasis. We collected data on demographics, the TNF inhibitor used, underlying inflammatory diseases, time to psoriasis onset after therapy initiation and lesion locations. Statistical analyses were performed using R, as shown in Table 1.

Among 93 patients with TNF inhibitor-induced psoriasis, 21 patients (22.6%) were diagnosed with psoriasis punctata after evaluation with clinical photographs and lesion descriptions (see Figure 1). The remaining 72 patients were categorised as the ‘other subtype’ group. Psoriasis punctata group had a younger average age at diagnosis (31.0 years) than the other subtypes (37.5 years). Sex proportions and the percentage of patients with pre-existing psoriasis were similar in both groups. Adalimumab and infliximab were most associated with psoriasis punctata (40.9% each), whereas adalimumab was most associated with other subtype psoriasis (56.9%). Average onset of psoriasis after starting TNF-alpha inhibitors was shorter in the psoriasis punctata group (19.0 months), than in the other subtype group (27.1 months), although this difference was statistically insignificant. Crohn's disease was the most common underlying condition in both groups (59.1% and 48.0%, respectively). Psoriasis distribution was similar in both groups, though psoriasis punctata lesions were more prevalent on the trunk and upper extremities, and less on the palms and soles (Figure 2). Notably, 66.7% of psoriasis punctata patients also presented with concurrent plaque psoriasis.

Psoriasis punctata lesions are often perifollicular and may show clinical and histologic overlap with pustular variants of psoriasis. Distinctive characteristics of psoriasis punctata include a scattered pinpoint rash that may present with an overlying scale. These lesions can occur on any part of the body and are typically smaller than those seen in guttate psoriasis. Previous literature has described various types of psoriasis [4], with only one case report describing a patient with a ‘follicular psoriasiform eruption’ [2]. Laga et al. [5] examined 16 biopsies from nine patients with psoriasiform eruptions on TNF-α inhibitors, revealing psoriasiform patterns, lichenoid/interface patterns and neutrophil-rich infiltrates affecting hair follicles. Biopsy results of our psoriasis punctata patients (n = 7) included follicular-based intra-epidermal pustules, follicular-based epidermal pustules in a background of psoriasiform dermatitis, psoriasis vulgaris and spongiotic dermatitis with eosinophils. Additionally, 4 out of 21 patients had descriptions or biopsy results indicating the presence of pustules.

In conclusion, we describe a highly distinctive and likely under-recognised morphologic subtype of TNF-inhibitor-induced psoriasis, best characterised as psoriasis punctata. One limitation of our study is the inability to determine whether this subtype coexists with pre-existing psoriasis or represents an early form of guttate psoriasis. Prospective studies would be necessary to confirm that this is more common in TNF-inhibitor-induced psoriasis than idiopathic psoriasis. Notably, most of our patients' rashes remained morphologically stable, and the onset of psoriasis following TNF inhibitor initiation, along with improvement after discontinuing the offending drugs, suggests a strong association between this condition and the use of TNF-alpha inhibitors. Although classifying this subtype may not alter treatment, the morphology can be a diagnostic clue in patients who develop a papular, scaly rash after starting TNF inhibitors. Early recognition can lead to timely discontinuation of the offending drug and optimisation of treatment, ultimately preventing diagnostic delays and unnecessary use of antibiotics or invasive procedures.

Reviewed and deemed IRB Exempt; Assurance: Federal Wide Assurance (FWA)#: 00006183 UVa IRB #1 Registration IRB#00000447 UVA IRB #3 Registration IRB#00010459.

The authors have nothing to report.

Dr. Flowers serves as a principal investigator for Abbvie, Acelyrin, AstraZeneca, Clinuvel, Regeneron/Sanofi and Sun Pharmaceuticals. He has served on advisory boards for Argenx, Bristol-Myers Squibb and Janssen. None of the biologic agents studied in this study were funded in the clinical context of the data presented.