Search

Paradoxical reaction (PR) occurs when a drug elicits a reaction contrary to what was expected. To clarify the clinical features and genetic background of individuals susceptible to PR, we analyzed the clinical course of patients in whom psoriatic eruptions worsened or newly developed during tumor necrosis factor (TNF) antagonist administration and the role of focal infections and genetic variations. Of 125 patients who received TNF antagonist therapy for psoriasis, acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), or palmoplantar pustular psoriasis (PPP), eight patients with PR were surveyed at our hospital Dermatology Department between 2010 and 2021. A survey was also done on six patients who received TNF antagonist therapy for Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and hidradenitis suppurativa and were referred to our department due to PR. Additionally, Sanger sequencing analysis was performed for all exons and flanking introns of IL36RN (interleukin 36 receptor antagonist), CARD14 (caspase recruitment domain-containing protein 14), and AP1S3 (adaptor-related protein complex 1 subunit sigma 3). The clinical assessment of the 14 patients demonstrated an average age at PR onset of 48.4 years, a male : female ratio of 5:9, and a mean administration period until onset of 9.2 months. The clinical types of PR were plaque psoriasis, PPP, GPP, pustulosis, acne, ACH, hair loss, and exacerbation of arthralgia. Histopathology revealed psoriasiform dermatitis in three patients. One patient continued TNF antagonist therapy. All of the patients with psoriasis and GPP had dental infections, suggesting that focal infection may be a risk factor of the development of PR following TNF antagonist therapy. Gene analysis demonstrated CARD14 gene variants associated with RA, CD, AS, or PPP in four patients. In addition, all of the patients with ACH and PPP experienced PR, suggesting that these diseases may predispose patients to PR to TNF antagonist therapy., (© 2021 Japanese Dermatological Association.)

Regarding appropriate timings of discontinuation and resumption of biologics for psoriasis patients before and after elective surgeries, an international consensus has yet to be reached. The Japanese Dermatological Association of Guideline and Safety Manual for the use of Biologic Agents in Psoriasis 2013 states that infliximab (IFX) and adalimumab (ADA) should be withheld at least 4 and 2 weeks, respectively, before surgery and can be restarted as neither postoperative infection nor delayed wound healing is recognized. We experienced three generalized pustular psoriasis (GPP) patients and one plaque-type psoriasis patient undergoing surgeries during tumor necrosis factor (TNF)-α blocker therapy. Three GPP cases experienced uneventful post-surgical course. One psoriasis vulgaris patient on IFX had a wound healing delay with deterioration of psoriatic plaques which was restored by restarting IFX. The timing of suspension and resumption of TNF-α blockers in all cases were determined following the Japanese guideline., (© 2015 Japanese Dermatological Association.)

Background: Vitamin D3 ointment and corticosteroid ointment are both used for the treatment of palmoplantar pustulosis (PPP). However, to date there is no systematic study of the efficacy of combination therapy for the treatment of PPP., Objective: We compared the efficacy of a topical combination therapy with vitamin D3 and a topical corticosteroid with that of topical corticosteroid alone in the treatment of PPP., Method: We evaluated left-right comparison study of the efficacy of a combination therapy consisting of maxacalcitol ointment and betamethasone butyrate propionate ointment (BBP), and monotherapy with BBP alone in 27 patients with PPP for 8 weeks., Results: The improvement in the symptom (erythema, pustules/vesicles, hyperkeratosis/scales) scores was high for the combination therapy. In particular, the improvement rate for pustules/vesicles at week 8 after the combination therapy was significantly higher than for the monotherapy (p < 0.05)., Conclusion: This combination regimen demonstrated that not only topical corticosteroids, but also topical vitamin D3 ointment, is useful for the treatment of PPP.

Biologics such as tumor necrosis factor (TNF) inhibitors are highly effective for treating severe psoriasis, and an increasing number of patients benefit from them. However, subsidiary subjects have arisen in the course of treatment which may directly impact the continued use of these drugs in a given case. In this article, we report two cases of psoriasis vulgaris refractory to treatment with both adalimumab and infliximab. We measured the serum drug concentration and absorbance value of antidrug antibodies using the sandwich enzyme-linked immunoassay method. Antibodies to adalimumab and infliximab were detected in both patients. The low drug concentration and adverse clinical response observed corroborated these findings. Dosage and concomitant medication are considered to be important factors influencing the development of antibody formation. Therapeutic drug monitoring and measurement of antidrug antibodies will assist in maintaining a clinical response and in optimizing the response of patients being treated with biological therapies. The use of concomitant immunosuppressive medication should be considered for patients who will be treated with their second TNF inhibitor after having developed antidrug antibodies against their first TNF inhibitor., (© 2013 Japanese Dermatological Association.)