Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Comparison of microinsulated needle radiofrequency and carbon dioxide laser ablation for the treatment of syringoma.

Syringoma is a benign adnexal tumor originating from the intradermal eccrine ducts and predominantly occurs in women at puberty or later in life. We present a case of a 30-year-old woman with a 2-year history of syringoma on her neck and axillar region. She was treated with two devices in a split manner. The right-sided lesions of the neck were treated with one session of 10,600-nm carbon dioxide (CO2 ) laser ablation. The left-sided lesions were treated with microinsulated needle radiofrequency (RF) three times. After treatment, the lesions treated with CO2 showed hypertrophic scar formation, but the other side lesions treated with microinsulated needle RF showed a marked reduction in the size and number of lesions, without any adverse effects such as scarring and hyperpigmentation related to epidermal damage. The treatment of syringoma with microinsulated needle RF, which is insulated at the point of epidermal contact, results in good cosmetic outcomes. Syringoma, microinsulated needle RF, CO2 laser.

Initial and 5-day positivity rate of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) in exposed inpatients within shared rooms during the omicron-variant dominant period.

In this observational study conducted in 2022, 12.3% of patients who shared a room with a patient positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) also had a positive polymerase chain reaction (PCR) test, either at initial screening or during a 5-day quarantine. Therefore, screening and quarantine are still necessary within hospitals for close-contact inpatients during the SARS-CoV-2 omicron-variant dominant period.

Tuberculous Lymphadenitis in a Patient Treated with Dupilumab: A Case Report.

Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis; the most common presentation is isolated chronic non-tender lymphadenopathy in young adults without systemic symptoms. Dupilumab is a fully human monoclonal antibody directed against interleukin-4 receptor-α that blocks the synergistic effects of interleukin-4 and interleukin-13 on allergic inflammation. Its well-known adverse events are allergic conjunctivitis, injection site reaction, and dupilumab facial redness. A 32-year-old female with severe atopic dermatitis was treated with dupilumab for 2 months at our clinic. She complained of multiple enlarged palpable lymph nodes on the right side of the neck and inguinal area for 2 months. Laboratory tests showed an increased total eosinophil count and immunoglobulin E level, as well as positive interferon-γ release assays. Radiological examination showed multiple low echoic and heterogeneous well-enhancing lymph nodes in level II, III, IV, and V of the neck. Histological examination revealed caseous necrosis and tuberculoid granuloma. The lymph node enlargements were completely relieved after antituberculosis treatment. The mechanism for the development of tuberculous lymphadenitis in a patient receiving dupilumab is not fully understood yet. In some previous studies, treatment with dupilumab suppressed the expression of genes related not only to T helper 2 and eosinophil response but also to proinflammatory responses. It could not inhibit the intracellular growth of Mycobacterium tuberculosis in macrophages, predisposing them to the development of tuberculous infection. To the best of our knowledge, this is the first report on the development of tuberculosis lymphadenitis in a patient treated with dupilumab.

Very Early Patch Stage of AIDS-related Kaposi Sarcoma: A Case Report.

Kaposi sarcoma (KS) is a vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV-8). AIDS-related KS has variable clinical courses ranging from mild disease presenting as an incidental finding to severe disease presenting as an aggressively progressing neoplasm that can lead to poor prognosis or even death. Typical clinical manifestation of KS is known as multiple cutaneous lesions on the extremities, trunk, and face with mucosal involvement. A 46-year-old male with AIDS complained of an erythematous patch on the right forearm which appeared 5 months ago. For a year, he was treated with antiretroviral drugs for AIDS. Physical examination revealed a 2.5-cm solitary erythematous patch only on the right forearm. Laboratory data revealed human immunodeficiency virus (HIV)-1 RNA of less than 40 copies/ml and a CD4 cell count of 264 cells/mm3. Histological examination revealed numerous slit-like spaces and vascular proliferation with primitive blood vessels dissecting between the collagen bundles and the dermis. Immunohistochemical staining showed positive HHV-8 nuclear staining of spindle cells. The histological features and positive HHV-8 immunohistochemical stain were consistent with the diagnosis of early patch stage of AIDS-related KS. KS can readily be misdiagnosed in early patch stage even by experienced clinicians, which leads to requirement of pathologic determination. On close inspection, it can be distinguished from other mimickers by its distinctive histologic features and immunohistochemical staining for HHV-8. Therefore, in cases of HIV-positive patients with clinically or histologically vascular-appearing mucocutaneous lesions, KS should be considered as a possible differential diagnosis.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

The Role of Collagen VI α6 Chain Gene in Atopic Dermatitis.

BACKGROUND: In a previous study, we carried out whole-exome sequencing to identify genetic variants associated with early onset atopic dermatitis (AD) in Koreans and found that collagen VI α6 chain (COL6A6) gene polymorphisms are associated. COL6A6 is one of the chains that makes up the triple helix of collagen VI, and little is known about its role in AD. OBJECTIVE: To identify how COL6A6 changes in AD and clarify its role. METHODS: Immunohistochemical staining for COL6A6 was performed on tissues of AD, other skin diseases, and healthy controls. Human keratinocytes and fibroblasts were exposed to inflammatory cytokines and cultured to evaluate changes in COL6A6 expression. COL6A6 small interfering RNA (siRNA) was transfected into cells to identify the role of COL6A6. RESULTS: Total COL6A6 mRNA was higher in AD than in controls. In AD tissues, COL6A6 mRNA decreased significantly in the epidermis compared to controls, whereas COL6A6 protein was increased in the dermis. In the cultured cells, COL6A6 mRNA was suppressed in the epidermis by interleukin (IL)-4 and IL-13, whereas COL6A6 protein was induced in the dermis. In the COL6A6 siRNA-transfected keratinocyte, mRNA of FLG, LOR, and CASP14 decreased compared to controls; in contrast, mRNA of MMP1 increased. CONCLUSION: The reduction of epidermal COL6A6 due to the genetic mutation can cause skin barrier damage and it can contributes to the early onset of AD. COL6A6 is induced by IL-4 and IL-13, and it may play a role in fibrotic remodeling and inflammatory processes, which are major features of AD.

Liquid-liquid phase reaction between crystal violet and sodium hydroxide: kinetic study and precipitate analysis.

To investigate reaction order and kinetic parameters of the reaction between crystal violet (CV) and sodium hydroxide (NaOH), various concentrations of the reactants were applied. The present work also verifies the unknown solid product produced under highly concentrated conditions. The reaction orders of CV and NaOH were determined to be 1 and 1.08 by pseudo rate method, respectively, with a rate constant, k, of 0.054 [(M-1.08) s-1]. In addition to pseudo rate method, the half-life approach was used to calculate the overall reaction order to verify the accuracy of pseudo rate method. The overall reaction order was determined to be 1.9 by the half-life method. The overall reaction order based on the two methods studied was approximately 2. The precipitate formation was observed when high concentrations of CV (0.01-0.1 M) and NaOH (1.0 M) were applied. Fourier transform infrared (FTIR) spectroscopy was used to compare the spectra of the precipitate generated and a commercial solvent violet 9 (SV9). Based on the FTIR spectra, it was confirmed that the molecular structure of the precipitate matched that of solvent violet 9.

Cardiovascular comorbidities of atopic dermatitis: using National Health Insurance data in Korea.

BACKGROUND: It is well known that atopic dermatitis (AD) is associated with other allergic diseases. Recentely, links to diseases other than allergic disease have also been actively studied. Among them, the results of studies regarding AD comorbidities, especially cardiovascular disease (CVD), have varied from country to country. OBJECTIVE: To analyze whether the risk of CVD is different between AD patients and healthy controls using Korean National Health Insurance Data. METHODS: We obtained data from 2005 to 2016 from the Korean National Health Insurance Research Database. Patients with one AD code and two AD-related tests codes were selected as AD patients, and age-and sex-matched controls to the AD patients were selected from among those without AD (1:5). Each group was investigated for accompanying metabolic syndrome (which contains hypertension, type 2 diabetes, and hyperlipidemia) and CVD (angina, myocardial infarction, peripheral vascular disease, and stroke) using ICD 10 codes. RESULTS: The incidence of metabolic diseases and CVD were significantly different between the AD and control groups. Using multivariable Cox regression, differences were adjusted for sex, age, and other CVD and metabolic diseases. As a result, not only metabolic disease, but also the CVD risk of AD patients was significantly higher than that of the control group. Patients with AD had as significantly higher risk of hyperlipidemia (hazard ratio [HR] = 33.02, p < 0.001), hypertension (HR = 4.86, p < 0.001), and type 2 diabetes (HR = 2.96, p < 0.001). AD patients also had a higher risk of stroke (HR = 10.61, p < 0.001), myocardial infarction (HR = 9.43, p < 0.001), angina (HR = 5.99, p < 0.001), and peripheral vascular disease (HR = 2.46, p < 0.001). Besides hyperlipidemia, there was no difference in risk according to AD severity. CONCLUSION: Patients with AD have a greater risk of CVD than those without AD.

A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world.

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Facial erythema after the treatment of dupilumab in SLE patient.

BACKGROUND: Dupilumab is a receptor antagonist binding to the alpha subunit of the interleukin-4 receptor. Through binding to it, dupilumab inhibits signaling of both IL-4 and IL-13, the representative Th2 biomarkers. Recently, in addition to the treatment effects for atopic dermatitis (AD), there is an emerging adverse event as facial erythema. CASE PRESENTATION: A twenty-seven-year-old female patient developed erythema and desquamation on the face and neck after dupilumab administration. She had AD on her arms, legs, and trunk before the treatment but there was no atopic clinical feature in her face and neck. With the treatment of dupilumab, her skin lesions of the body have improved from the beginning of the treatment. In the patch test, including dupilumab, there was no specific finding other than the 1+ response to neomycin on day 2. In the intradermal test to dupilumab, a positive result was observed 15 min later, but negative both days 1 and 2. The blood examination showed an elevation of both ANA as 1:80 and anti-phospholipid antibodies (Anti-cardiolipin IgM, IgG, and Anti- beta 2 GPI IgG). She was diagnosed with Systemic lupus erythematosus (SLE) based on diagnostic criteria by a rheumatologist. CONCLUSION: Dupilumab is an emerging therapeutic agent for AD, and treatment cases are increasing in Korea. However, there are several adverse events during the treatment of dupilumab. Herein, we report the unexpected adverse event during the treatment of dupilumab in SLE patients.

Retrospective Study of Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Korea: Efficacy and Safety of Dupilumab in Real-World Practice.

Among biological agents for the treatment of atopic dermatitis (AD), dupilumab is a front-runner. Although many studies have been conducted on the real-world use of dupilumab, the sample size is often small and data is primarily on Western people. Therefore, we investigated the efficacy and safety of dupilumab in patients with moderate-to-severe AD in Korea. All patients with moderate-to-severe AD treated with dupilumab from September 2018 to June 2019 in this institution were included and analyzed by medical records. They were evaluated using the Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI), respectively on admission, after two weeks (only EASI and NRS) and after 16 weeks. Laboratory tests were measured before and 16 weeks after treatment. A total of 101 patients were included. All efficacy tools showed a significant decrease after 16 weeks; EASI 77.4%, NRS 70.0%, POEM 60.7%, and DLQI 65.0%. EASI was characterized by a marked improvement of 51.5% in just two weeks. The treatment response was not significantly different according to the interval of treatment. Elevated Lactate Dehydrogenase (LDH) at 16 weeks was associated with poor treatment response. Moreover, a high eosinophil count was related to a lower change in EASI and POEM. In the correlation analysis, EASI was not correlated to DLQI before treatment. For changes after 16 weeks, POEM showed the highest correlation with DLQI. (R = 0.66, p < 0.001) In the additional analysis for factors affecting treatment response, the female gender was associated with good treatment response. (odds ratio = 5.4, p = 0.04) Adverse events from treatment included facial erythema (9.9%) and conjunctivitis (5.0%). Overall, it was confirmed that the efficacy of dupilumab in the real-world is similar to that of the existing clinical trials. We suggest that POEM is a useful tool for identifying the quality of life. The female gender was associated with a good treatment response. Both an elevated LDH and a high eosinophil count could be a therapeutic biomarker. Further research will be needed for a long-term period.