Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE). OBJECTIVE: We sought to identify overlapping and unique PPP, palmPP, and DPE drivers to provide molecular insight into their pathogenesis. METHODS: We performed bulk RNA sequencing of lesional PPP (n = 33), palmPP (n = 5), and DPE (n = 28) samples, as well as 5 healthy nonacral and 10 healthy acral skin samples. RESULTS: Acral skin showed a unique immune environment, likely contributing to a unique niche for palmoplantar inflammatory diseases. Compared to healthy acral skin, PPP, palmPP, and DPE displayed a broad overlapping transcriptomic signature characterized by shared upregulation of proinflammatory cytokines (TNF, IL-36), chemokines, and T-cell-associated genes, along with unique disease features of each disease state, including enriched neutrophil processes in PPP and to a lesser extent in palmPP, and lipid antigen processing in DPE. Strikingly, unsupervised clustering and trajectory analyses demonstrated divergent inflammatory profiles within the 3 disease states. These identified putative key upstream immunologic switches, including eicosanoids, interferon responses, and neutrophil degranulation, contributing to disease heterogeneity. CONCLUSION: A molecular overlap exists between different inflammatory palmoplantar diseases that supersedes clinical and histologic assessment. This highlights the heterogeneity within each condition, suggesting limitations of current disease classification and the need to move toward a molecular classification of inflammatory acral diseases.

A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement.

BACKGROUND: In plaque psoriasis, palmoplantar areas are more difficult to treat. OBJECTIVE: Evaluate the safety and efficacy of risankizumab (RZB) versus placebo (PBO) for the treatment of palmoplantar psoriasis. METHODS: Patients were randomized to RZB or PBO for 16 weeks followed by RZB through week 52. The primary and secondary end points were achievement of palmoplantar Investigator's Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (ppIGA 0/1), achievement of ≥75%, ≥90%, and 100% improvement in Palmoplantar Psoriasis Area and Severity Index (PPASI 75, PPASI 90, PPASI 100) and achievement of static Physician Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (sPGA 0/1) at week 16. Safety was based on treatment-emergent adverse events. RESULTS: RZB demonstrated significant efficacy compared to PBO at week 16 in the patients achieving ppIGA 0/1 (33.3% vs 16.1% [P = .006]), PPASI 75 (42.5% vs 14.9% [P < .001]), PPASI 90 (27.6% vs 5.7% [P < .001]), sPGA 0/1 (32.2% vs 11.5% [P < .001]), and PPASI 100 (17.2% vs 1.1% [P < .001]). Results improved through week 52 with no new safety signals. LIMITATION: No biologic comparator. CONCLUSIONS: RZB demonstrated good tolerance and efficacy in palmoplantar psoriasis.

Palmoplantar psoriasis: A clinicopathological correlation in a tertiary care hospital.

BACKGROUND: Palmoplantar psoriasis is a clinical variant of psoriasis characterized by well-defined erythematous desquamating plaques on palms and soles, which may or may not include pustules. Hyperkeratotic lesions of palm and sole commonly include Psoriasis, Eczema and Tinea. These conditions often present with overlapping clinical and histopathological features requiring clinicohistopathological correlation for a conclusive diagnosis. The presence of munro's microabscess or spongiform pustule of kogoj differentiates psoriasis of palm and sole from other hyperkeratotic lesions of palm and sole. The objective of this study was to study the clinical and histopathological profile of palmoplantar psoriasis and correlate clinical diagnosis with histopathological diagnosis. METHOD: A hospital-based, descriptive study was conducted from January 1, 2020, to December 31, 2020. Fifty-two patients were clinically diagnosed as palmoplantar psoriasis with or without involving other parts of body and routine histopathological evaluation was carried out as per standard protocols. RESULT: Clinically diagnosed 52 cases of palmoplantar psoriasis showed varied histopathology with hyperkeratosis (100%), parakeratosis (100%), regular acanthosis (75%), Supra-papillary thinning (44.2%), spongiosis (65.4%), tortuous vessels in the papillary dermis (78.8%) and mixed inflammatory infiltrates (predominantly lymphocytic-100%), which were observed to be prominent findings in skin biopsies of our patients. Clinicopathological correlation was achieved in 88.5% of cases. CONCLUSION: This study shows clinically diagnosed palmoplantar psoriasis with histopathological features consistent with palmoplantar psoriasis in 88.5% cases. Thus, clinically inconclusive hyperkeratotic lesions with palmoplantar psoriasis can be diagnosed with histopathological correlation improving the therapeutic intervention.

Paradoxical psoriasis induced by IL-17 inhibitors: a case series of patients with axial spondyloarthritis and a systematic literature review.

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient's psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

BACKGROUND AND OBJECTIVE: The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. PATIENTS AND METHODS: Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. RESULTS: A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. CONCLUSIONS: Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

IL-36α and IL-36γ expressions in the differential diagnosis of palmoplantar psoriasis and palmoplantar eczema: A retrospective histopathologic and immunohistochemical study.

BACKGROUND: Diagnosing hyperkeratotic lesions on the palms and soles is often challenging for both clinicians and pathologists. Interleukin (IL)-36 cytokines play an important role in the pathogenesis of psoriasis. METHODS: We retrospectively re-evaluated hematoxylin-eosin-stained biopsy specimens of 30 patients with clinically diagnosed palmoplantar psoriasis (PP) and 30 patients with palmoplantar eczema (PE), and then performed IL-36α and IL-36γ immunohistochemistry. RESULTS: Among the histopathologic features, thinning of the rete ridges and vertical alternation of parakeratosis and orthokeratosis had the highest positive predictive value (PPV) in diagnosing PP (72.7% and 69.3%, respectively). Immunohistochemically, patients with PP predominantly showed diffuse or focal strong expression with IL-36α and IL-36γ staining in the upper layers of the epidermis (86.7% and 83.3%, respectively). The comparison of the mean IL-36α and IL-36γ expression scores significantly differed between PP and PE (P < .001). Among all histopathologic and immunohistochemical features, diffuse strong expression of IL-36α and IL-36γ staining had the highest PPVs in favor of a diagnosis of PP (75% and 76.7%, respectively). CONCLUSIONS: Our data suggest that IL-36α and IL-36γ immunohistochemistry can be used in the differential diagnosis of PP and PE.

Safety and efficacy profile of oral cyclosporine vs oral methotrexate vs oral acitretin in palmoplantar psoriasis: A hospital based prospective investigator blind randomized controlled comparative study.

Palmoplantar psoriasis (PPP) is a variant of psoriasis which affects only 5% body surface area, but has a devastating impact on affected individual's quality of life. There are few studies assessing efficacy of individual drugs, and few comparative studies of efficacy of two drugs in the literature, however randomized control trial comparing all three drugs against each other has not been done. A total of 75 patients of PPP were enrolled for study and randomly divided into three groups A, B, C of 25 each and assigned for treatment with cyclosporine (CSA) (2.5-5 mg/kg/d), methotrexate (MTX)(7.5-15 mg/week), and acitretin (ACT) (25-50 mg/d), respectively. Modified psoriasis area and severity index (PASI), psoriasis severity scale, visual analogue scale, physician global assessment, and PPQOL were used for monitoring response to therapy and improvement in quality of life up to end of study, and thereafter monthly follow-up was done to find duration of remission for next 90 days. Side effects if any were recorded. There was a statistically significant difference in modified PASI for CSA, MTX, and ACT. The mean modified PASI at baseline was 12.8 ± 4.8 for CSA, 12.57 ± 3.8 for MTX, and 11.92 ± 3.28 for ACT (P = .75). Mean modified PASI reduced to 2.91 ± 1.8 for CSA, 6.57 ± 2.2 for MTX, and 4.7 ± 2.2 for ACT at week 5 (P = <.01). Mean modified PASI further reduced to 0.095 ± 0.35 for CSA, 2.12 ± 1.4 for MTX, and 0.78 ± 0.97 for ACT at end of study (P = <.01). However, average duration of remission was 9 weeks for ACT group, followed by 6.47 and 3 weeks for CSA and MTX group, respectively. Adverse events were comparatively more in ACT group as compared to MTX and CSA groups. PPP affects quality of life tremendously and warrants systemic treatment for the same. CSA provides fastest resolution of lesions and have highest efficacy. MTX and ACT have similar efficacy, but ACT provides longer duration of remission.

Efficacy of oral methotrexate (MTX) monotherapy vs oral MTX plus narrowband ultraviolet light B phototherapy in palmoplantar psoriasis.

Palmoplantar psoriasis (PPP) is a chronic, inflammatory dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. We aim to compare the effect of oral methotrexate (MTX) monotherapy vs MTX plus narrowband ultraviolet light B (NB-UVB) in the treatment of recalcitrant PPP. This was a comparative clinical trial involving 90 patients of PPP. Eligible patients were randomly assigned to one of the two treatment groups. We aim patients in group A received 10 mg oral MTX weekly, and patients in group B received oral MTX 10 mg weekly and NB-UVB sessions twice weekly for 12 weeks. There was a statistically significant difference in reduction of modified PPP Area Severity Index (m-PPPASI) of patients in MTX plus NB-UVB at week 12. The mean m-PPPASI at week 12 was 3.66 ± 2.11 in MTX plus NB-UVB group and 6.51 ± 2.04 in MTX only group (P < .001). Marked improvement (m-PPPASI 75) was achieved in 20 (44.44%) patients in MTX plus NB-UVB group compared with 6 (13.3%) in MTX monotherapy group (P < .001). Combination of MTX and NB-UVB phototherapy helps to attain a better clinical response (reduction in m-PPPASI score) than MTX monotherapy in the treatment of recalcitrant PPP.

Real world data from the use of secukinumab in the treatment of moderate-to-severe psoriasis, including scalp and palmoplantar psoriasis: A 104-week clinical study.

Several clinical studies demonstrated the safety and efficacy of the interleukin-17 inhibitor secukinumab in the systemic treatment of moderate-to-severe psoriasis, as well as psoriatic arthritis (PsA) in adults, whereas real-world data is limited. A single-center clinical study was performed to evaluate in real-world practice the efficacy of secukinumab up to Week 104 of treatment in moderate-to-severe chronic plaque psoriasis, including scalp and palmoplantar involvement, according to Physician Global Assessment (PGA), PASI75/90/100 and scalp, and palmoplantar PGA. Drug survival, the safety profile of secukinumab, and patient's quality of life were also assessed during a 2-year observation period. Out of 83 patients included, 56.3% were biologic-naïve, and 94% had scalp, 25.3% palmoplantar, and 43.9% joint involvement. At Week 16, PASI75/PASI90/PASI100 were observed in 83.8/70.0/46.3%, respectively. Scalp and palmoplantar PGA were rapidly improved, with 98.7 and 95.5%, respectively, reaching clear/almost clear skin at Week 16. After 104 weeks, drug survival was 74.5%. A significant improvement of the quality of life was observed. Biologic-naïve patients without coexisting PsA benefited the most. Real-world data demonstrated secukinumab efficacious in chronic plaque psoriasis, including specific locations such as scalp and palmoplantar psoriasis with a safety profile similar to that in clinical trials.

How frequently does palmoplantar psoriasis affect the palms and/or soles? A systematic review and meta-analysis.

INTRODUCTION: Palmoplantar psoriasis (PPP) is a variant of psoriasis that affects the palms and/or soles. Although PPP is a disabling and therapeutically challenging condition, its epidemiology is poorly defined. AIM: To assess the prevalence of PPP locations (palms, soles or both), and to analyse epidemiological and clinical characteristics of the disease. MATERIAL AND METHODS: Two bibliographic databases (MEDLINE and SCOPUS) were used as data sources searched from inception to October 2017. The selection of articles was limited to human subjects and English or French languages. RESULTS: A search resulted in a total of 293 articles, out of which 24 were utilized for the current systematic review and 21 for meta-analysis. All listed studies comprised a total of 2083 patients with PPP, with more males than females. According to the results of meta-analysis, majority of patients had the highest prevalence of both palms and soles involvement (95% CI: 47-67), with an almost equal prevalence showing palmar (21%; 95% CI: 13-30) or plantar (20%; 95% CI: 12-29) involvement. The most prevalent type of PPP was plaque/hyperkeratotic, followed by the pustular type. CONCLUSIONS: Almost three-fifths (59%) of all PPP patients had involvement of both palms and soles, while exclusive palmar or plantar involvement was seen in 21% and 20% of patients, respectively. Future research should be performed to elucidate basic epidemiological and clinical characteristics of PPP, which would be helpful for proper consideration of this condition.

Comparison of effectiveness and safety of excimer lamp vs topical calcipotriol-clobetasol propionate combination in the treatment of palmoplantar psoriasis.

BACKGROUND: Very few studies have assessed the efficacy of excimer in the treatment of palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol-clobetasol propionate combination. PURPOSE: To compare the effectiveness and safety of excimer lamp vs topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP. METHODS: This right-left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol-clobetasol combination (once daily) on another side for 12 weeks, followed by 8 weeks of follow-up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (mPPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP). Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤25%), mild (>25%-50%), moderate (>50%-75%), and marked (>75%). Secondary outcome measures were the proportion of patients achieving >75% reduction in mPPPASI and the time taken to achieve it. RESULTS: Of 36 recruited patients, 33 completed treatment and 21 adhered to 8-weeks follow-up. The mean mPPPASI on the excimer-treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (P < .001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow-up). The mean mPPPASI on the calcipotriol-clobetasol combination treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (P < .001) and 2.70 ± 3.97 at 12th week and 20th week, respectively. The reduction was significant for both treatment and the difference between the two was not statistically significant. Minimal, mild, moderate, and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol-clobetasol combination, respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4, and 8 weeks in 1, 2, and 8 patients, respectively, using either modalities. The adverse effects (most commonly hyperpigmentation) were noted more frequently on the excimer-treated sides; however, they were well tolerated. CONCLUSION: Both excimer lamp and calcipotriol-clobetasol propionate combination are equally effective in the treatment of PPP.

Psoriasis in special localizations.

Psoriasis is a chronic inflammatory dermatosis affecting 1-3% of the general population. Patients with psoriasis represent a heterogeneous population with individual disease expression - different degrees and severity of skin involvement. Psoriatic lesions in particular localizations such as the face, scalp, intertriginous or palmoplantar areas significantly reduce quality of life. Patients often feel ashamed, embarrassed, or self-conscious about their symptoms. Furthermore, genital psoriasis significantly affects sexual health. Among patients with psoriasis, the prevalence of special localizations is estimated to be 23-27% on the nails, 49% on the face, 12-16% on the palms and soles, and up to 36% in intertriginous regions. Due to peculiar features of skin in these areas, adequate and specific management is required, which is discussed in this review.

Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from GESTURE, a randomized controlled trial.

BACKGROUND: Plaque psoriasis affecting palms and soles is disabling and often resistant to treatment. OBJECTIVE: Evaluate the efficacy and safety of secukinumab, an anti-interleukin 17A antibody, in subjects with palmoplantar psoriasis. METHODS: In this double-blinded, randomized controlled trial, 205 subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The primary endpoint was Palmoplantar Investigator's Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16. RESULTS: At week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the percentage achieved with placebo (1.5%, P < .001). Palmoplantar Psoriasis Area and Severity Index (ppPASI) was significantly reduced with secukinumab 300 mg (-54.5%) and 150 mg (-35.3%) compared with placebo (-4.0%, P < .001). Dermatology Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups were also significantly higher compared with placebo at week 16 (P < .01) and pain and function of palms and soles was markedly improved with secukinumab as measured by the palmoplantar Quality-of-Life Instrument. Secukinumab 300 mg consistently showed the best outcomes. The safety profile was favorable and similar to previous studies. LIMITATIONS: Lack of active comparator. CONCLUSION: In GESTURE, the largest randomized controlled trial in palmoplantar psoriasis, secukinumab demonstrated the greatest efficacy to date for treating difficult-to-treat psoriasis.

Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis.

BACKGROUND: Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. OBJECTIVE: We evaluated the efficacy and safety of apremilast in palmoplantar psoriasis. METHODS: A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1). RESULTS: Significantly more patients taking apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group (P < .001); 59% of the apremilast group had a PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving placebo (P < .001). LIMITATIONS: This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. CONCLUSION: Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.