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Immunocompromised individuals, primarily attributable to using immunosuppressants, face heightened COVID-19 risks. Despite the proven efficacy of COVID-19 vaccines, their impact on patients with immune-mediated dermatological diseases remains unclear. This study aims to thoroughly examine vaccine immunogenicity, effectiveness, and safety in immune-mediated dermatological disease patients. Clinical studies in adults that compared vaccinated immune-mediated dermatological disease patients with vaccinated healthy controls or unvaccinated immune-mediated dermatological disease patients in terms of vaccine immunogenicity, COVID-19 infection, adverse events, or exacerbation of immune-mediated dermatological diseases were searched via electronic databases. Seventeen studies (1,348,690 participants) were included. Seroconversion rates between immune-mediated dermatological disease patients and healthy controls were not different. However, among individuals aged ≤55 years, immune-mediated dermatological disease patients had lower mean anti-SARS-CoV-2 IgG levels. Immunosuppressed immune-mediated dermatological disease patients also had lower titres and were less likely to achieve T-cell response. In terms of safety, the risk of adverse events was higher in atopic dermatitis patients, but those with psoriasis had a reduced risk. Additionally, immunosuppressed patients had fewer adverse events. Vaccinated immune-mediated dermatological disease patients had a lower risk of COVID-19 infection than unvaccinated patients but a higher risk than healthy controls; however, disease exacerbation may be induced. In conclusion, immune-mediated dermatological diseases showed a reduced vaccine response in our meta-analysis, yet vaccination remained effective against COVID-19 infection and well tolerated.
Subject(s)
COVID-19 Vaccines , COVID-19 , Immunocompromised Host , Immunogenicity, Vaccine , Skin Diseases , Humans , COVID-19 Vaccines/immunology , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , COVID-19/immunology , Skin Diseases/immunology , SARS-CoV-2/immunology , Vaccine Efficacy , Middle Aged , AdultABSTRACT
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.
Subject(s)
Allopurinol , Polymorphism, Single Nucleotide , Humans , Allopurinol/adverse effects , Male , Female , Thailand , Middle Aged , Case-Control Studies , Aged , Adult , Pharmacogenetics , HLA-B Antigens/genetics , Genetic Predisposition to Disease , Pharmacogenomic Variants , Southeast Asian PeopleABSTRACT
Panitumumab is a recombinant, fully humanized immunoglobulin G2 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is approved for the first- and second-line treatment of advanced wild-type KRAS colorectal cancer. Although common cutaneous side effects include acneiform dermatitis, folliculitis, and xerosis, ocular toxicities have occasionally been reported. Herein, we report the case of an 81-year-old Thai female with chemorefractory advanced stage sigmoid colon cancer who developed isolated periorbital dermatitis following treatment with panitumumab plus modified FOLFOX6. The cutaneous adverse reaction recurred after subsequent infusions; however, it was alleviated by topical therapy. To our knowledge, panitumumab-induced periorbital dermatitis is exceptionally rare. To raise awareness of potential periocular cutaneous side effects in patients taking EGFR inhibitors, the published literature regarding periorbital dermatitis induced by these agents has also been reviewed in this article. Periorbital dermatitis should be considered as a potential cutaneous reaction following panitumumab administration, and should be promptly treated.
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Behçet's disease (BD) manifests as an autoimmune disorder featuring recurrent ulcers and multi-organ involvement, influenced by genetic factors associated with both HLA and non-HLA genes, including TNF-α and ERAP1. The study investigated the susceptible alleles of both Class I and II molecules of the HLA gene in 56 Thai BD patients and 192 healthy controls through next-generation sequencing using a PacBio kit. The study assessed 56 BD patients, primarily females (58.9%), revealing diverse manifestations including ocular (41.1%), vascular (35.7%), skin (55.4%), CNS (5.4%), and GI system (10.7%) involvement. This study found associations between BD and HLA-A*26:01:01 (OR 3.285, 95% CI 1.135-9.504, P-value 0.028), HLA-B*39:01:01 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-B*51:01:01 (OR 3.033, 95% CI 1.135-8.103, P-value 0.027), HLA-B*51:01:02 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-C*14:02:01 (OR 3.485, 95% CI 1.339-9.065, P-value 0.01), HLA-DRB1*14:54:01 (OR 1.924, 95% CI 1.051-3.522, P-value 0.034), and HLA-DQB1*05:03:01 (OR 3.00, 95% CI 1.323-6.798, P-value 0.008). However, after Bonferroni correction none of these alleles were found to be associated with BD. In haplotype analysis, we found a strong linkage disequilibrium in HLA-B*51:01:01, HLA-C*14:02:01 (P-value 0.0, Pc-value 0.02). Regarding the phenotype, a significant association was found between HLA-DRB1*14:54:01 (OR 11.67, 95% CI 2.86-47.57, P-value 0.001) and BD with ocular involvement, apart from this, no distinct phenotype-HLA association was documented. In summary, our study identifies specific HLA associations in BD. Although limited by a small sample size, we acknowledge the need for further investigation into HLA relationships with CNS, GI, and neurological phenotypes in the Thai population.
Subject(s)
Behcet Syndrome , Female , Humans , Behcet Syndrome/epidemiology , HLA-DRB1 Chains/genetics , High-Throughput Nucleotide Sequencing , HLA-C Antigens/genetics , Thailand , HLA-B Antigens/genetics , Alleles , Technology , Genetic Predisposition to Disease , Aminopeptidases/genetics , Minor Histocompatibility AntigensABSTRACT
The intradermal route has emerged as a dose-sparing alternative during the coronavirus disease 2019 (COVID-19) pandemic. Despite its efficacy in healthy populations, its immunogenicity has not been tested in immune-mediated dermatologic disease (IMDD) patients. This assessor-blinded, randomized-controlled, non-inferiority trial recruited patients with two representative IMDDs (i.e., psoriasis and autoimmune bullous diseases) to vaccinate with fractionated-dose intradermal (fID) or standard intramuscular (sIM) BNT162b2 vaccines as a fourth booster dose under block randomization stratified by age, sex, and their skin diseases. Post-vaccination SARS-CoV-2-specific IgG and interferon-γ responses measured 4 and 12 weeks post-intervention were serological surrogates used for demonstrating treatment effects. Mean differences in log-normalized outcome estimates were calculated with multivariable linear regression adjusting for their baseline values, systemic immunosuppressants used, and prior COVID-19 vaccination history. The non-inferiority margin was set for fID to retain >80% immunogenicity of sIM. With 109 participants included, 53 received fID (all entered an intention-to-treat analysis). The fID demonstrated non-inferiority to sIM in humoral (mean outcome estimates of sIM: 3.3, ΔfID-sIM [mean, 95%CI]: -0.1, -0.3 to 0.0) and cellular (mean outcome estimates of sIM: 3.2, ΔfID-sIM [mean, 95%CI]: 0.1, -0.2 to 0.3) immunogenicity outcomes. Two psoriasis patients from the fID arm (3.8%) developed injection-site Koebner's phenomenon. Fewer fID recipients experienced post-vaccination fever (fID vs. sIM: 1.9% vs. 12.5%, p = 0.027). The overall incidence of disease flare-ups was low without a statistically significant difference between groups. The intradermal BNT162b2 vaccine is a viable booster option for IMDD patients troubled by post-vaccination fever; its role in mitigating the risk of flare-ups remains unclear.
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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.
Subject(s)
Drug Hypersensitivity , Humans , Middle Aged , Drug Hypersensitivity/diagnosis , beta-Lactams/adverse effects , Immunologic Tests , Enzyme-Linked Immunospot Assay , Patch TestsABSTRACT
BACKGROUND: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs). METHODS: The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated. RESULTS: Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE. CONCLUSIONS: Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.
Subject(s)
HIV Infections , Stevens-Johnson Syndrome , Humans , Male , Female , Young Adult , Adult , Middle Aged , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , HLA-DRB1 Chains/genetics , Cicatrix , HLA-B Antigens/genetics , Stevens-Johnson Syndrome/genetics , HLA-A Antigens/genetics , PhenotypeABSTRACT
Bullous systemic lupus erythematosus (BSLE) is a rare blistering skin manifestation of systemic lupus erythematosus (SLE). Dapsone is reported to be helpful in mild-to-moderate BSLE cases; however, its use may be limited or prohibited due to particular complications such as drug hypersensitivity, dose-dependent hemolytic anemia, and other significant hematologic abnormalities. Rituximab, an anti-CD20 monoclonal antibody, has been reported with off-label use in BSLE patients, but data are still limited. Hence, our objective is to explore the efficacy of rituximab among these patients. Herein, we report a 21-year-old Thai woman presented with blistering eruption on the oral cavity, scalp, trunk, and extremities for 1 month. The investigations revealed a positive direct Coomb's test, an elevated erythrocyte sedimentation rate (ESR), and a positive antinuclear antibody (ANA). Skin biopsy showed focal interface dermatitis. Direct immunofluorescence (DIF) illustrated mixed linear and granular deposition of immunoglobulin (Ig)G, IgM, IgA, and C3 along the dermo-epidermal junction (DEJ). Enzyme-linked immunosorbent assay (ELISA) showed circulating antibodies to type VII collagen. She was diagnosed with severe BSLE and autoimmune hemolytic anemia (AIHA) refractory to several oral immunosuppressants but was successfully treated with rituximab. The authors also performed a review of the literature on prior BSLE cases managed with rituximab.
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Sclerodermic or scleroderma-like lupus erythematosus panniculitis (SLEP) shares both clinical and histopathological features between lupus panniculitis and localized scleroderma. It is exceedingly rare. We herein report a case of SLEP manifested with a solitary, firm-to-hard, erythematous plaque in an Asian woman. This patient responded well to intralesional corticosteroid and antimalarials. We have reviewed the pathogenesis of fibrosis in patients with chronic cutaneous lupus erythematosus as well as documented cases of SLEP in the literature.
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Background: By depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines' humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear. Objective: To estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients. Methods: This retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2. Findings: Forty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients. Conclusions: Nine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Immunoglobulin G , Retrospective Studies , Rituximab/adverse effects , SARS-CoV-2ABSTRACT
BACKGROUND: Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce. OBJECTIVES: To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination. METHODS: This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination. RESULTS: Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD. CONCLUSIONS: Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.
Subject(s)
Autoimmune Diseases , COVID-19 Vaccines , COVID-19 , Psoriasis , Humans , Antibodies, Viral , COVID-19 Vaccines/adverse effects , Drug-Related Side Effects and Adverse Reactions , Immunosuppressive Agents/adverse effects , Prospective Studies , SARS-CoV-2 , Vaccination/adverse effectsABSTRACT
Pemphigus and lupus erythematosus are both B-cell-mediated autoimmune diseases, dependent on autoreactive CD4+ T lymphocytes to modulate autoimmune B-cell response. Many forms of pemphigus have been reported to occur in association with systemic lupus erythematosus (SLE) as well as other autoimmune diseases. However, it remains unclear whether this association occurs because of a shared immunopathogenesis or the coexistence may be coincidental. We hereby present a case report of discoid lupus erythematosus and paraneoplastic pemphigus associated with marginal zone lymphoma in a 54-year-old Thai man who had persistent oral erosions for 1 year together with generalized polymorphic cutaneous eruptions for 2 months. Simultaneous occurrence of paraneoplastic pemphigus and discoid lupus erythematosus without SLE has never been reported in the same individual. Hydroxychloroquine, immunosuppressive agents including prednisolone and azathioprine together with chemotherapy were given to treat these conditions.
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Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) are uncommon inflammatory skin disorders that occasionally share clinicopathological features. Differentiating between the two entities remains problematic, and a definitive diagnosis usually requires multi-step investigations, which is an enormous challenge to physicians. We hereby report a rare case of a 22-year-old female patient diagnosed with PLEVA who later developed LyP type F, a new histological variant of LyP. Our report highlights that long-term follow-up is essential to determine associated hematologic malignancies, particularly in cases with recalcitrant or progressive cutaneous lesions of PLEVA and/or LyP.
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Objective: To investigate the prevalence of low vitamin D levels in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) in Thailand and determine the influential factors associated with inadequate levels. Methods: The medical records of patients diagnosed with SLE and/or CLE and evaluated for serum 25-OH vitamin D were retrospectively reviewed from January 2014 to January 2021. Vitamin D deficiency (<20 ng/mL) and insufficiency (21-29 ng/mL) were indicated, and predictors of hypovitaminosis D were identified by multiple linear regression analysis. Results: In total, 414 patients with SLE and/or CLE were included in the study. Vitamin D deficiency was predominant in the CLE-only group (33.3%), followed by SLE without CLE (15.6%) and SLE with CLE (8%), p < 0.001. Likewise, vitamin D insufficiency was more prevalent in the CLE-only group (44.4%) compared to SLE with (35.8%) and without CLE (40%). Multivariate analysis showed that a higher SLEDAI-2K score and female sex had a negative association with vitamin D levels, while an intake of every 10,000 IU of vitamin D2 per week increased serum vitamin D levels by up to 2.37 ng/mL. Furthermore, forty-five percent of patients continued to have vitamin D depletion despite commencing the recommended doses of vitamin D replacement. Conclusion: Approximately half of Thai patients with SLE and 80% of CLE had vitamin D inadequacy. Vitamin D replacement is a good predictor of high serum vitamin D levels, while lower serum levels were associated with higher disease severity. Therefore, serum vitamin D monitoring and supplementation are suggested for all lupus erythematosus cases, especially those with CLE.
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INTRODUCTION: Scalp biopsy is a standard method for the definitive diagnosis of alopecia. The hair count parameters of each scalp area remain unclear. This study aimed to determine hair count values at different scalp locations from histopathology and to establish reference values for each part of the scalp. METHODS: We obtained biopsy specimens from the frontal, vertex, temporoparietal, and occipital areas of the scalps of normal deceased subjects. All specimens were evaluated for the number of follicular units, hair counts, hair types, and stages of the hair cycle. RESULTS: In total, 240 specimens were collected from 60 cadavers. Across all scalp sites, the temporoparietal area showed the lowest mean hair count, number of follicular units, terminal and vellus hairs, and terminal-to-vellus hair ratio. The average anagen-to-telogen hair ratio was comparable across all scalp sites. This study did not observe a significant association of hair parameters with gender differences or increasing age in all scalp areas. CONCLUSIONS: The present study revealed the diversity of the hair index among different scalp areas and suggested that normal hair count values should be separately standardized on each scalp region. Our findings may provide useful reference values for the histopathological evaluation of hair disorders in Asians.
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Reports of immune-related adverse events caused by programmed cell death-ligand 1 (PD-L1) inhibitor have been emerging. Herein, we report a subacute cutaneous lupus erythematosus (SCLE)-like eruption presented after the treatment of durvalumab in a patient with extensive-stage small cell lung carcinoma. A 74-year-old Thai man was referred to our department after experiencing multiple dusky red to brownish papules and patches with scale and erosions on photo-distributed areas after receiving 3 infusion cycles of durvalumab. Histological finding revealed epidermal atrophy with interface changes and superficial perivascular infiltration of lymphocytes. Serum antinuclear antibodies (ANA) was 1:320 and anti-Ro/Sjogren's-syndrome-related antigen A (anti-Ro/SSA) antibodies were positive (2+). Based on the history and clinicopathological correlation, the diagnosis of SCLE-like eruption due to durvalumab was made. To the best of our knowledge, this is the first case of durvalumab-induced SCLE.
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BACKGROUND: Melasma is a complex and multipathophysiological condition that is challenging to treat. The roles of each element in the dermis were highlighted in this recent year due to targeting it with emerging therapies. Although some studies have demonstrated abnormal findings in the dermis of melasma lesions, there are no integrated data regarding these findings. PURPOSE: This article aims to discuss each finding in the dermis of melasma lesions and to provide some ideas about treatment options. METHODS: An Internet search was completed using the MEDLINE, Embase, Scopus, and Google Scholar databases for relevant literature through June 2021 and reference lists of respective articles. Only the articles published in English language were included. RESULTS: Several studies have focused on the dermal changes in melasma. Common findings included basement membrane disruption, pendulous melanocytes, marked solar elastosis, increased melanophages, increased mast cells, and neovascularization. In addition, each of them had the specified mechanism that may relate with the others. CONCLUSION: Several changes in the dermis of melasma lesion may be connected with pathological changes in the epidermis. This may serve as a potential target treatment for melasma, which requires a multimodal approach.
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INTRODUCTION: Intramuscular corticosteroids (IMC) have gained popularity for the treatment of severe alopecia areata (AA) in recent years; however, evidence on their efficacy and safety is still limited. OBJECTIVE: To evaluate the efficacy, relapse rate, and tolerability of IMC in the treatment of AA, as well as factors associated with treatment outcomes. METHODS: Time-to-event analysis was performed on patients with severe, extensive, or rapidly progressive AA receiving IMC. The IMC regimen comprised triamcinolone acetonide 20-40 mg/mL injected every 4-6 weeks. The evaluated outcomes included initial (25% regrowth), significant (75% regrowth), and complete hair regrowth (100% regrowth). Relapse and adverse events were also noted. Factors associated with treatment outcomes and relapse were analyzed using the Cox proportional hazards model. RESULTS: A total of 101 patients were eligible for analysis. Significant hair regrowth was obtained in 80.2% of the patients (n = 81), in a median time of 3.4 months (95% confidence interval [CI] = 2.9-4.4). Complete hair regrowth was achieved in 48.5% of the subjects (n = 49), and relapse was observed in 47.5% (n = 48). Acneiform eruption was the most common adverse effect. Multivariable analysis revealed that nail involvement was a negative predictor of significant hair regrowth (adjusted hazard ratio [HR] = 0.04, 95% CI = 0.01-0.55; P = 0.015), whereas duration of AA longer than 6 months was associated with disease recurrence (adjusted HR = 4.02, 95% CI = 1.52-4.66; P = 0.005). CONCLUSION: This study demonstrated the efficacy and safety of IMC in the treatment of severe or active AA; however, the relapse rate remained relatively high after discontinuation of the therapy. Nail involvement was a negative predictor of significant hair regrowth, while disease duration longer than 6 months predicted AA relapse.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Alopecia Areata/drug therapy , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Hair and scalp involvement is prevalent in connective tissue diseases (CTDs). Trichoscopic features may provide a diagnostic implementation and enable differentiation among CTDs; however, a direct comparison of these signs among CTD patients is lacking. OBJECTIVES: To compare trichoscopic findings in dermatomyositis (DM), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) as well as determine their distinctive features and associations with disease activity. METHODS: Trichoscopic photographs were taken from DM, SLE, and SSc patients and further evaluated for hair shaft and scalp surface abnormalities. Data regarding patients' clinical manifestations, laboratory results, and disease activity were analyzed. RESULTS: One hundred fifty participants, consisting of 30 DM, 60 SLE, and 60 SSc patients, were included. Perifollicular red-brown pigmentation, brown scattered pigmentation, and white patches were exclusive findings in DM, SLE, and SSc, respectively (p < 0.001). A multinomial logistic regression analysis revealed that DM demonstrated higher odds for having microaneurysmal blood vessels than SLE and SSc (odds ratio [OR] = 22.22, 95% confidence interval [CI] = 1.73-285.13, p = 0.017, and OR = 15.34, 95% CI = 1.36-177.59, p = 0.029, respectively). Polymorphic vessels forming a telangiectatic network suggested SSc over SLE (OR = 12.83, 95% CI = 1.35-121.98, p = 0.026), while avascular areas were more pronounced in SSc than DM and SLE (OR = 43.24, 95% CI = 5.17-361.67, p = 0.001, and OR = 0.03, 95% CI = 0.01-0.24, p = 0.001, respectively). In a quantile regression analysis, perifollicular red-brown pigmentation, reduction in hair diameter, and the absence of thin arborizing vessels were linked to higher disease activity in DM, SLE, and SSc, respectively (all p < 0.05). CONCLUSIONS: Trichoscopy is a valuable tool possessing diagnostic and prognostic values for CTDs. Specific trichoscopic features allow adequate distinction between DM, SLE, and SSc and may help identify active disease.
Subject(s)
Dermatomyositis , Lupus Erythematosus, Systemic , Pigmentation Disorders , Scleroderma, Systemic , Dermatomyositis/complications , Hair , Humans , Lupus Erythematosus, Systemic/complications , Scalp , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnostic imagingABSTRACT
BACKGROUND: Oral lupus erythematosus (OLE) and oral lichen planus (OLP) are among the common causes of oral lichenoid lesions (OLLs). The differential diagnosis among causes of OLLs, particularly between OLE and OLP, is challenging as they have significant clinical and histopathological overlap. OBJECTIVES: To compare and summarize the clinical, histopathological, and direct immunofluorescence (DIF) findings between OLE, OLP, and other OLLs and to explore the diagnostic value of CD123 immunohistochemistry. METHODS: A retrospective study on patients with OLE, OLP, and other OLLs was performed between January 2014 and December 2019. The baseline characteristics, the clinical, histopathological, and DIF features, as well as CD123 immunohistochemistry for plasmacytoid dendritic cells (PDCs) were statistically analyzed and compared between groups. RESULTS: Of 70 patients, 12 had OLE, 39 had OLP, and 19 had other OLLs. Oral erosions/ulcers were the most common findings in all three groups. Red macules, telangiectases, and discoid plaques were more common in OLE patients, while OLP cases were typified by reticulated patches (p < 0.05). Additionally, white patches were found more often in other OLLs than in both OLE and OLP (p = 0.002). Histologically, mucosal atrophy, basal vacuolization, and perivascular infiltrate were observed in OLE, whereas OLP specimens possessed mucosal hyperplasia, hypergranulosis, and compact orthokeratosis (p < 0.05). Mucosal spongiosis was a histologic feature that favored other OLLs over OLE and OLP (p < 0.001). Data on DIF were nonspecific for all three conditions. For immunohistochemical staining, the median number of total CD123+ PDCs was observed to be higher in OLE than OLP in the mucosal-submucosal junction (MSJ) (p = 0.021), the superficial perivascular area (p = 0.026), and the superficial and deep perivascular areas (p = 0.001). Likewise, PDCs in clusters ≥2+ were seen in significantly higher numbers on OLE than OLP along the MSJ (p = 0.002), the superficial perivascular area (p < 0.001), as well as the superficial and deep perivascular areas (p = 0.011). CD123+ PDCs were found to be significantly more numerous in both OLE and OLP than other OLLs in all of the abovementioned areas (all p < 0.05). CONCLUSION: While there are some differences in the clinicopathological features between OLE, OLP, as well as other OLLs, a significant overlap remains. The quantity and distribution pattern of CD123 immunohistochemical staining has a diagnostic implication in differentiating OLE from OLP and other OLLs.