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.

Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians.

Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.

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.

Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors.

BACKGROUND: Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. OBJECTIVES: The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. METHODS: A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. RESULTS: A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. CONCLUSIONS: 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

Acitretin treatment in antimalarial-refractory/intolerant discoid lupus erythematosus: A prospective, open-label, uncontrolled study.

BACKGROUND: The treatment of discoid lupus erythematosus (DLE) is often challenging, especially in patients who are refractory or intolerant to topical treatments and first-line systemic drugs, specifically antimalarial drugs. Although acitretin has been shown to be effective in patients with DLE in a few studies, there is no published study describing the long-term efficacy of acitretin with a validated score. OBJECTIVES: To evaluate the efficacy and safety of acitretin in patients with antimalarial-refractory/intolerant DLE. METHODS: A prospective, open-label, uncontrolled study was conducted in patients with antimalarial-refractory/intolerant DLE. All patients were treated with an initial dosage of 10 mg acitretin daily. Clinical response was assessed using the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) at weeks 4, 8, 12, and 24. Acitretin was increased to 25 mg daily unless an adequate response was achieved at week 8. RESULTS: Fourteen patients were recruited. Of these, 10 were antimalarial-refractory and four were antimalarial-intolerant. The acitretin therapy was discontinued in one patient after 20 weeks of treatment because of active systemic disease. Of the 13 remaining patients, the mean RCLASI activity scores declined from 21 ± 9 at baseline to 9 ± 4 at week 24. A significant reduction in RCLASI was initially observed at week four and consistently noted at each follow-up visit (p ≤ 0.01). At the end of the study, a marked response was achieved in approximately 80% of patients. There were no statistically significant differences in the clinical response or in the requirement of the up-dosing of acitretin between the refractory and intolerance groups (p = 0.88 and p = 0.326, respectively). Age ≥50 years old, female sex, and generalized DLE were the favorable prognostic factors. No serious adverse events were noted. CONCLUSIONS: Acitretin appears to be an effective treatment with acceptable safety profiles for antimalarial-refractory/intolerant DLE.

Real-world experience of secukinumab in moderate to severe psoriasis patients in Thailand: Characteristics, effectiveness, and safety.

Secukinumab demonstrated high efficacy and favorable safety profile in patients with moderate-to-severe plaque psoriasis (PsO) in clinical trials. However, understanding of patient characteristics and clinical outcomes in real world in Thailand is still limited. To describe patient characteristics, effectiveness and safety of secukinumab in Thai PsO patients. This retrospective study analyzed data from medical records of adult PsO patients who initiated secukinumab at 7 dermatology centers from September 2017 to April 2021. Study outcomes included patient characteristics and changes in Psoriasis Area and Severity Index (PASI) score from baseline at weeks 4 and 16 after secukinumab initiation. Adverse events were recorded. Subgroup analyses by adherence rate and completeness of loading dose were performed. Of 163 patients, the mean (SD) age was 44.0 (14.0) years. Most patients (84.7%) were previously treated with topical therapy while 62.0% and 21.5% of patients had received systemic and biologic therapy, respectively. The mean baseline PASI score was 15.4 (9.3). Overall, the mean PASI score improved by 58.0% at week 4 and 78.4% at week 16. Statistically significant differences in PASI approvement were revealed among subgroups of patients with different loading dose and adherence rate. Adverse effects were reported in 8.0% of patients. The characteristics of patients in this study were slightly different from clinical trials in terms of demographic and clinical characteristics, as well as PsO treatment. Secukinumab was effective and safe in Thai patients with PsO, especially among those with complete loading dose and a higher adherence rate.

A case of dengue fever presenting with acute urticaria.

BACKGROUND: Acute urticaria (AU) is characterized by the occurrence of spontaneous wheals, angioedema, or both for less than 6 weeks. Viral infection is considered to be one of the common causes of AU, however AU has never been reported in association with dengue infection. OBJECTIVE: To describe the first case of AU in dengue virus infection. METHODS: Case report. RESULTS: A 17-year-old healthy male presented with first episode of AU which associated with confirmed dengue virus infection. He responded well with antihistamine treatment and without recurrence at 2-month follow up. CONCLUSIONS: Patients with dengue virus infections can present with AU, possibly from viral-infected mast cell. Future research will have to clarify this association.

Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report.

Cronkhite-Canada Syndrome (CCS) presents with gastrointestinal polyposis and the triad of cutaneous abnormalities including nail dystrophy, alopecia, and hyperpigmentation of the skin. The etiology is not well understood. The histology of skin lesion in CCS has not been routinely described. Especially, the nail matrix pathology has not been reported. In this study, the authors report the nail matrix pathology in a patient with CCS. Interestingly, the histologic evaluation revealed matrix hypergranulosis. Because matrix hypergranulosis is commonly found in several inflammatory nail diseases, this discovery points out that an inflammatory process is probably one of the important pathogeneses in CCS.

Clinical features of chronic urticaria in aging population.

BACKGROUND: Different clinical features of skin diseases have been addressed between aging patients and non-aging patients. However, data focusing on the clinical features of chronic urticaria (CU) in aging patients especially in the Asian population are still limited. OBJECTIVE: This study aimed to investigate the clinical characteristics of CU in aging and non-aging patients in the Asian population. METHODS: Case records of 1622 CU patients attending the Urticaria Clinic, Department of Dermatology, Siriraj Hospital, Mahidol University, Thailand between 2000 and 2013 were retrospectively reviewed. All CU patients older than 60 years were recruited. Twice the number of CU patients who were non-aging were enrolled using a systematic sampling method. RESULTS: Of the 1622 CU patients, 67 (4.1%) were aging patients. From these, 134 non-aging patients with CU were recruited. The majority of patients for both groups were female, with 67.2% and 77.6% of the aging and non-aging groups, respectively. In both groups, the most common cause of CU was chronic spontaneous urticaria. In the aging group, positive autologous serum skin test, anti-thyroid antibodies and antinuclear antibodies were found more commonly than in the non-aging group, without a statistically significant difference. The mean duration of the disease tended to be shorter in the aging group. CONCLUSION: Our study showed that CU in aging patients was uncommon (4.1%). Aging patients with CU seemed to have shorter disease duration and higher percentages of autoantibodies than non-aging patients with CU without a statistically significant difference.

Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome.

Background: A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS - including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies - remain unknown. Objective: To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS. Methods: Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1ß, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis. Results: The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS. Conclusions: These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08-7.035), C*03:04 (OR = 3.665, 95%CI: 2.102-6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326-3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions.

Reactive neutrophilic dermatoses associated with nontuberculous mycobacterial infection in adult-onset immunodeficiency syndrome responded well to acitretin: four cases report.

BACKGROUND: Recent articles have suggested an adult-onset immunodeficiency syndrome that was described in HIV-uninfected adults with disseminated non-tuberculous mycobacterial infection and/or another opportunistic infection with concomitant reactive dermatoses. Few studies reported the drugs used to treat these reactive neutrophilic dermatoses including systemic steroid, etretinate, clofazimine, colchicine, and dapsone. This study aims to report the efficacy of acitretin for the treatment of this condition. MATERIAL AND METHOD: Four HIV-uninfected patients with disseminated non-tuberculous mycobacterial infection and the reactive dermatoses from department of internal medicine, Maharaj Nakorn Chiang Mai Hospital between 2008 through 2011 were observed in the clinical presentation and course of disease including treatment and response. RESULTS: All patients had at least one episode of reactive dermatoses with variable presentations comprising Sweet's syndrome with pustules, pustular vasculitis-like lesions, or generalized pustular lesions. Acitretin was prescribed to treat these reactive neutrophilic dermatoses. It showed a good response without side effects. CONCLUSION: Acitretin, a second-generation retinoid, can be used for the treatment of reactive pustular lesions in the syndrome of adult-onset immunodeficiency due to its good response, being well tolerated, and without immunosuppression.

Clinical Outcomes, Patient-Reported Outcomes, and Economic Burden for Thai People Living with Chronic Urticaria (CORE-CU) in routine practice: A study protocol for a monocentric prospective longitudinal study.

BACKGROUND: Few prospective longitudinal studies have been conducted in Thailand to account for the long-term response to chronic urticaria (CU) treatment, clinical outcomes, and patient-reported outcomes (PROs) among people living with CU based on routine practice. As such, a prospective longitudinal study will be conducted to better understand the long-term responses to treatment options and the burden of disease in Thai CU patients. METHODS AND DESIGN: This study is a routine clinical practice registry-based, monocentric, prospective, observational longitudinal study in the northern region of Thailand. Adult patients in an outpatient clinic diagnosed with CU, including both chronic spontaneous urticaria and chronic inducible urticaria will be recruited for this study. The cohort will be collected and registered using the joint routine clinical practice data based on multiple datasets including claims outpatient and inpatient data, routine laboratory results, medication utilization, health care costs, clinical characteristics, long-term urticaria care and monitoring, and PRO measures. The point prevalence of adverse health outcomes will be estimated and reported corresponding to 95% confidence intervals (95% CIs). The overall trend analysis will be analyzed to explore the effect of over time across the cohort time frame. CONCLUSION: This prospective longitudinal study will report the clinical outcomes, PROs, and economic burden among Thai people living with CU based on routine clinical practice. Findings will provide comprehensive evidence and could facilitate best practices for CU care management for health care professionals, researchers, policymakers, and public society. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR, thaiclinicaltrials.org) registration TCTR20210706005. Registered on July 6, 2021.