Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study.

Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13-8.04; p = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49-4.34; p < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21-4.41; p = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82-33.7; p < 0.001). Kaplan-Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.

Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients.

BACKGROUND: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. METHODS: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. RESULTS: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10- 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10- 27). CONCLUSIONS: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.

A retrospective analysis of 65 patients with acrodermatitis continua of Hallopeau.

There are limited data on acrodermatitis continua of Hallopeau (ACH), particularly among Asian populations. The primary aim was to evaluate the clinical features of ACH and treatment approaches in a sizeable multicentre Asian cohort. We analysed data from adult patients diagnosed with ACH. Of 65 patients with ACH, seven patients had ACH with GPP. Females were more frequently affected in both conditions. Five (71.4%) developed GPP 5-33 years after ACH onset, while two (28.6%) developed GPP concurrently with ACH. The onset age for ACH with GPP (27.9 ± 13.6 years) was earlier than that of isolated ACH (39.8 ± 17.3 years). Metabolic comorbidities were common. ACH exhibited a chronic persistent course. Among systemic non-biologics, acitretin was the most frequently prescribed, followed by ciclosporin and methotrexate. Acitretin and ciclosporin demonstrated similar marked response rates, which surpassed that of methotrexate. Regarding biologics, a marked response was more commonly observed with interleukin-17 inhibitors than with tumour necrosis factor inhibitors. Females are predominant in both conditions. The onset age for ACH among Asian patients is earlier (late 30s) than that for Caucasian patients (late 40s). Interleukin-17 inhibitors may be more effective than tumour necrosis factor inhibitors in managing ACH.

The Steatosis-Associated Fibrosis Estimator (SAFE) score for assessing significant liver fibrosis in patients with psoriasis.

BACKGROUND: There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis. OBJECTIVES: To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference. METHODS: We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did. CONCLUSIONS: The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice.

IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity.

BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

Unveiling the role of neutrophils in chronic spontaneous urticaria: Beyond mast cells.

Mast cells and eosinophils are considered pivotal contributors to the pathogenesis of chronic spontaneous urticaria (CSU). However, emerging evidence suggests that neutrophils also play a central role. Cutaneous mast cells and macrophages orchestrate the recruitment of neutrophils through the regulation and activation of diverse processes, including heightened local vascular permeability and chemokine release. Studies have demonstrated increased activation and elevated levels of neutrophil-related cytokines in CSU patients. Moreover, neutrophils have been proposed as antigen-presenting cells during the late-phase reaction of immunoglobulin E-mediated allergy and have been associated with the expression of calcitonin gene-related protein and vascular endothelial growth factor in CSU. Histopathological analysis of lesional skin in CSU patients revealed significantly higher eosinophil and neutrophil counts than unaffected skin. However, the extent of neutrophil infiltration in the skin does not appear to correlate with the number of neutrophils in peripheral blood. The utility of the neutrophil-lymphocyte ratio as a marker for disease activity or remission in CSU remains inconclusive. Neutrophil-targeted therapy may confer benefits for CSU patients who exhibit resistance to antihistamines. Omalizumab has demonstrated its ability to reduce neutrophil counts, the neutrophil-lymphocyte ratio, and the neutrophil-monocyte ratio in peripheral blood. While dapsone and colchicine are recommended as alternative treatment options for CSU, their evidential support from published studies remains limited. Inhibitors targeting interleukin-1 and neutrophil-related cytokines have been proposed as potential therapeutic interventions for patients exhibiting neutrophil predominance. Further research is warranted to gain deeper insights into the involvement of neutrophils in CSU and to explore potential therapeutic interventions.

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative.

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Prevalence and clinical characteristics of pruritus, and the factors significantly associated with high pruritic intensity in patients with psoriasis: a cross-sectional study.

Despite the significant prevalence of pruritus in psoriasis, its pathogenesis remains unknown, and research on pruritus in Thai psoriasis patients is limited. Objectives: The objective was to investigate the prevalence and clinical characteristics of pruritus, and the factors significantly associated with high pruritic intensity in Thai psoriasis patients. Material and methods: In a cross-sectional study design, pruritus data were collected from the medical records of patients who attended an outpatient psoriasis clinic in Thailand between 2020 and 2021. Results: The overall prevalence of pruritus was 81.2% among 314 psoriasis patients. Psoriasis patients with pruritus had higher Psoriasis Area Severity Index and Dermatology Life Quality Index scores than those without pruritus. The legs, back, arms, and scalp were the most common areas for pruritus. Pruritus was relieved with topical emollients, topical corticosteroids, and oral antihistamines in 66.3, 63.1, and 52.9% of patients, respectively. Female sex, psoriasis body surface area greater than or equal to 10%, and genital psoriasis were factors that independently predicted high pruritus intensity. Conclusion: Psoriasis patients should be screened and treated for pruritus to improve both psoriasis treatment outcomes and patient quality of life. Further studies are needed to clarify the most effective medications for pruritus in patients with severe psoriasis.

Potential Therapeutic Approaches for Chronic Urticaria: Beyond H1-Antihistamines and Biologics.

Chronic urticaria is a disease that can significantly impact a patient's quality of life and ability to function. There are effective treatment options, such as nonsedating antihistamines or biologics, but some patients do not respond to these therapies, or the therapies are not available or affordable to all patients. This review aims to summarize potential treatment strategies for patients (1) who do not respond to antihistamines and (2) cannot readily access or do not respond to biologics. The review emphasizes the importance of sound clinical practice, including correct diagnosis of chronic urticaria phenotypes, treatment of associated comorbidities, and consideration of add-on pharmacological and nonpharmacological approaches. Although some treatments may lack high-quality evidence, they may still be justifiable in certain cases, provided that there is shared decision-making, regular reassessment, and early recognition of adverse events.

Acrodermatitis continua of Hallopeau and generalised pustular psoriasis: Should they be the same or different entities?

Pustular psoriasis is characterised by eruptions of neutrophilic sterile pustules. The European Rare and Severe Psoriasis Expert Network consensus defines pustular psoriasis into three subtypes; generalised pustular psoriasis (GPP), palmoplantar pustulosis and acrodermatitis continua of Hallopeau (ACH). Mixed forms are categorised according to their predominant features. However, the Japanese Dermatological Association includes ACH under the diagnosis of GPP. This article aims to review the similarities and differences between ACH and GPP. Based on our review, interleukin (IL)-36RN mutations, the most frequent genetic findings in pustular psoriasis are found most commonly in GPP, followed by ACH. Genotypes of IL-36RN mutations among GPP patients and ACH patients are different between European and Asian ethnicities. IL-36 signalling pathway is the main mechanism. Metabolic diseases are common comorbidities and joint involvement can occur in 20.5%-36.4% of both conditions. Associated plaque psoriasis is more common in GPP than in ACH. Generally, ACH, even the generalised type, does not have systemic inflammation whereas GPP can occur with or without systemic inflammation. ACH can occur before, simultaneously, or after the development of GPP. However, response to treatment for GPP and ACH even in the same patients appear to be different. ACH seemed to be more recalcitrant to treatment than GPP but severe flare of GPP can lead to morbidity and mortality. Although GPP and ACH share genotypes and pathogenesis, we believe that ACH should be classified separately from GPP, and not under diagnosis of GPP. Future research is warranted to satisfactorily distinguish the two conditions.

Do different platforms of coronavirus vaccines have different impacts on psoriasis flares?

This study evaluated the impacts on psoriasis flares of 3 vaccine platforms: inactivated, viral vector and mRNA. Respectively, 198 and 96 psoriasis patients with and without COVID-19 vaccination during the study period. Group comparison revealed no increased risk of psoriasis flaring after COVID-19 vaccination. The vaccinated group received 425 doses of vaccine (140 inactivated, 230 viral vector and 55 mRNA). Patients' self-reported symptoms included all three platforms causing psoriasis flare, but the highest was among patients administered with mRNA vaccines. Most flares were mild to moderate, and most patients (89.8%) managed their flare-up lesions without rescue therapy. In conclusion, our study showed that the rate of psoriasis flare was not significantly different between vaccinated and unvaccinated groups. Factors that might explain psoriasis flare include vaccine-related psychological stress and side effects from vaccination. Different platforms of corona vaccines seemed to have different impact of psoriasis flares. Based on our results and the recommendations of several consensus guidelines, the benefits of COVID vaccinations outweigh the risks to patients with psoriasis. Patients with psoriasis should receive a COVID vaccine as soon as one is available.

The validity and reliability of a Thai version of the Angioedema Control Test: Which recall period is preferable?

BACKGROUND: The Angioedema Control Test (AECT) is a questionnaire that monitors disease control in patients with angioedema, with a recall period of 4 weeks (AECT-4wk) or 3 months (AECT-3mo). OBJECTIVE: This study investigated the psychometric properties of a Thai version of the AECT. METHODS: Of 54 patients, 46, 5, 2, and 1 had recurrent angioedema with chronic spontaneous urticaria, hereditary angioedema, idiopathic histaminergic angioedema, and acquired angioedema due to C1 esterase inhibitor deficiency, respectively. The AECT, Angioedema Activity Score (AAS), Dermatology Life Quality Index (DLQI), Angioedema Quality of Life Questionnaire (AE-QoL), and anchors for disease control (numeric rating scale [NRS] and patient global assessment-Likert scale [PatGA-LS]) were used. The patients rated the efficacy of their treatment. RESULTS: Fifty-four and 47 patients completed the AECT-4wk and AECT-3mo, respectively. Both AECT versions showed significant correlations with disease activity (AAS, r = 0.6-0.8), disease control (NRS and PatGA-LS, r = 0.7-0.9), and quality of life impairment (DLQI and AE-QoL, r = 0.6-0.8). Higher correlations were found for the AECT-4wk than for the AECT-3mo. Excellent internal consistency (alpha = 0.98 and 0.97, respectively) and intraclass correlation (0.96 and 0.94, respectively) were found. A cutoff ≥ 10 was confirmed to identify patients with well-controlled disease for both AECT versions (AUCs = 0.89 and 0.97). CONCLUSIONS: The Thai version of the AECT is a valid and reliable tool for clinical practice. Due to the shorter recall period, the AECT-4wk may be more accurate than, and preferable to, the AECT-3mo. A cutoff ≥ 10 should be used to identify patients with well-controlled disease.

An analysis of psoriasis hospitalisation in Thailand.

Psoriasis hospitalisation is not frequently reported. The objective of this study was to determine (1) the clinical, laboratory and treatment features of patients with psoriasis hospitalised due to flare-up and (2) other causes of admission of patients with psoriasis. We retrospectively reviewed data on 48 patients admitted due to psoriasis flare-up and 1908 patients with psoriasis admitted due to concomitant illnesses or comorbidities. The study period was 2005-2021. The latter group was compared with 821,804 patients without psoriasis admitted during the period. Of the 48 cases, 37.5% had erythroderma, and 62.5% had generalised pustular psoriasis (GPP). Women (68.8%) predominated, especially in the GPP group (76.7%). The mean age of admission with erythroderma (44.8 years) was higher than for GPP (32.1 years). Infection was the main trigger for psoriasis flare-up (46%). Abnormalities in liver function tests were found in 33.3% of the cases. These abnormalities usually subsided 1-2 months after skin improvement (83.4%). Acitretin was the most prescribed drug for GPP (81.4%), whereas topical treatment alone (50%) was the most frequent erythroderma therapy. Intensive care was needed by 9.3% of patients with GPP. In the psoriasis group admitted due to concomitant illnesses or comorbidities, admission due to digestive and infectious causes was significantly higher for psoriasis patients. Our study showed that trend of psoriasis admission due to disease flare-up was not significantly changed even in the era of biologics. We believed that patient education on avoiding the common precipitating factors of psoriasis flare-up and good self-care is mandatory to reduce the risk of hospitalisation.

Prevalence of Depressive Symptoms and Their Impact on Perceived Stress and Quality of Life Among Patients with Psoriasis.

Objective: This study aimed to investigate the prevalence of depressive symptoms in patients with psoriasis and the association between depressive symptoms, perceived stress level, and quality of life of the participants. Methods: Patients with psoriasis were invited to complete the Thai versions of the Patient Health Questionnaire, Perceived Stress Scale-10, Psoriasis Disability Index, and Simplified Psoriasis Index. To identify significantly related factors of depression, the independent sample t-test or Mann-Whitney U-test was performed to compare continuous variables between groups, and the chi-square test or Fisher's exact test was used to compare categorical variables between groups. The association between the severity of depression and other variables was examined using Spearman's correlation coefficient. Results: Of the 150 participants assessed, 32 (21.3%) had depressive symptoms. Elevated stress scores, subjective psychosocial impact of psoriasis, self-perceived current severity of psoriasis, and impaired quality of life were significantly associated with depressive symptoms. Depressive symptom severity was determined to be positively correlated with perceived stress, quality-of-life impairment, current severity, and the psychosocial impact of psoriasis. Conclusion: Depressive symptoms are prevalent among patients with psoriasis. Those with high scores for perceived stress, a psychosocial impact of psoriasis, or disease severity should be evaluated for depression, as it can hamper their quality of life.

Do Antinuclear Antibodies Influence the Clinical Features of Chronic Spontaneous Urticaria?: A Retrospective Cohort Study.

Background: Antinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described. Objectives: To compare clinical features of CSU patients who are positive and negative for ANA. Methods: This was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until July 2021. All patients were investigated for ANA. Clinical feature data was compared between CSU patients with positive ANA and negative ANA groups using the 2-sample t-test and the Mann-Whitney U test for quantitative variables. The chi-squared test or Fisher's exact test was conducted to explore the association of qualitative variables. Disease relapse and remission were analysed via Kaplan-Meier survival analysis. Results: Of 323 CSU patients, 31% had positive ANA. There were no significant differences in disease severity or impairment in quality of life. Patients with a positive ANA test had significantly lower prevalence of allergic rhinitis (p = .048) and significantly higher level of erythrocyte sedimentation rate (p = 0.007). Kaplan-Meier survival analysis showed that 2% of ANA positive CSU patients achieved remission status after one year and 28% did so after five years. There was no statistically significant difference in time to remission and time to relapse between ANA-positive and negative groups. Conclusion: Positive ANA in CSU patients could not indicate the differences in main disease characteristics from the ANA-negative CSU patients. Investigation for ANA may be useful in CSU patients who are suspected of having autoimmune diseases.

Natural history and clinical course of patients with dermographism in a tropical country: a questionnaire-based survey.

Background: Dermographism is the most common form of chronic inducible urticaria. However, the natural history and clinical course of patients with dermographism in tropical countries has not fully been described. Objective: To examine clinical features, natural history and clinical course of dermographism in Thai patients according to their experiences. Methods: A cross-sectional, internet-based survey was conducted in 2021. All study respondents completed a 45-item questionnaire that was circulated on social media regarding dermographism. Results: Among the 2,456 respondents who reported dermographism, 1,900 had symptomatic dermographism (SD), while 556 had simple dermographism (SimD). Of the respondents who reported SD and SimD, the female to male ratio was 2.2:1 and 2.4:1, respectively. The median age of the first episode of SD and SimD was 16 and 15 years, respectively. Older age, greater body weight, cardiovascular diseases, allergic conjunctivitis, atopic dermatitis, changes in temperature, and family history of dermographism were all factors linked to an increased probability of SD. Half of the respondents with SD reported moderate itch severity. Moreover, about half of SD and almost all of SimD respondents let the wheal resolve on its own. Second generation H1-antihistamines were most commonly prescribed while over-the-counter medicines were taken by both SD and SimD respondents. Conclusion: This survey highlights several aspects of dermographism in Thai patients which can be useful for healthcare providers. SD is troublesome and affects the quality of life of many patients, leading some to seek medication themselves.

The Anti-Psoriatic Efficacy and Safety Profile of Topical and Intralesional Methotrexate: A Literature Review.

Methotrexate (MTX) has long been considered the first-line oral systemic pharmacotherapy for psoriasis. The drug has several well-known systemic side effects, such as bone marrow suppression and hepatotoxicity. To avoid them, the use of topical or intralesional administrations of MTX has become an interesting option. With the advent of novel drug delivery systems, especially nanocarriers, the usage of a high-efficacy and safe topical MTX for psoriasis has nearly been attained. This review examined the development, anti-psoriatic efficacy and adverse effects of topical forms of MTX (plain MTX; MTX with chemical enhancer; MTX using nanotechnology; MTX with protein transduction domains; MTX with liquid crystalline systems; and MTX with physical enhancer/laser) and intralesional MTX in psoriasis patients and psoriasis-induced animals. The efficacy of topical MTX varied with the drug delivery technology employed. Nevertheless, the overall safety profile of the topical forms was favourable. A 25 mg/mL MTX solution injected intralesionally at the nail matrix worked well for nail psoriasis recalcitrant to topical treatment. To improve the standard of care for patients with psoriasis, randomized controlled trials that establish the most effective MTX-delivery system are needed.