Generalized lymphatic anomaly (GLA), previously known as lymphangiomatosis, is a rare developmental disease characterized by abnormal proliferation of lymphatic vascular structures that may involve the dermis, soft tissue, bone, and visceral parenchyma. Being an uncommon condition and the lack of specific symptoms often result in a delayed diagnosis or even misdiagnosis, which, in addition to its progressive nature, can lead to dysfunction of vital organs, and ultimately, a poor prognosis. In this report, we present a unique case of GLA in an upper Egyptian female child. Increasing awareness of the possible phenotypic presentations of such anomalies can lead to early diagnosis and possibly more effective management before significant organ damage ensues.

Inborn errors of immunity (IEI) can affect different parts of the immune system and manifest especially through pathological infection susceptibility and immune dysregulation. Cutaneous manifestations of IEI can hint at the underlying immunodeficiency and the tendency for infection and inflammation. These manifestations can present as recurring eczema, erythema, abscesses, and hair loss with poor response to therapy. Cutaneous manifestations can be specific for certain IEI, or rather unspecific. Together with clinical course and severity, they can indicate the diagnosis. Early and accurate recognition, diagnosis, and treatment are crucial for optimizing patient outcomes. The diagnosis can be determined through a detailed patient history, clinical examination, and immunological diagnostics. Collaboration between immunologists and dermatologists is vital for comprehensive care and improvement of life quality.
UNASSIGNED: Primäre Immundefekte (PID) können verschiedene Aspekte des Immunsystems betreffen und sich insbesondere durch pathologische Infektionsanfälligkeit und Immundysregulation zeigen. Hautmanifestationen bei PID können auf eine zugrunde liegende Immunschwäche und eine erhöhte Anfälligkeit für Infektionen und Entzündungen hinweisen. Diese Hautsymptome präsentieren sich unter anderem als rezidivierende Ekzeme, Erytheme, Abszesse und Haarausfall mit schlechtem Therapieansprechen. Die kutanen Manifestationen können zum Teil morphologisch hinweisend auf einen bestimmten PID sein oder sind bei unspezifischen Symptomen mit dem Verlauf und dem Schweregrad zusammen wegweisend für die Diagnosestellung. Eine rechtzeitige Diagnose und angemessene Behandlung sind entscheidend, um Komplikationen zu vermeiden. Die Diagnosestellung erfolgt in der Regel durch eine detaillierte Anamnese, körperliche Untersuchung und immunologische Diagnostik. Eine enge Zusammenarbeit zwischen Immunologen, Pädiatern und Dermatologen ist wichtig, um eine optimale Versorgung der Patienten zu gewährleisten und die Lebensqualität zu verbessern.

OBJECTIVE: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc.
METHODS: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies.
RESULTS: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash.
CONCLUSIONS: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations.

UNASSIGNED: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed.
UNASSIGNED: Treatment options were reviewed, and opinions were provided for most facets of jSSc including general management, some of which differs from adult systemic sclerosis, such as the use of corticosteroids, and specific organ involvement, such as skin, musculoskeletal, pulmonary, and gastroenterology.
UNASSIGNED: We are suggesting the treat to target strategy to treat early to prevent cumulative disease damage in jSSc. Conclusions are derived from both expert opinion and available literature, which is mostly based on adult systemic sclerosis (aSSc), given shared pathophysiology, extrapolation of results from aSSc studies was judged reasonable.

BACKGROUND: To investigate the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement.
METHODS: Sera of 194 SSc patients from the Leiden CCISS cohort, fulfilling ACR/EULAR 2013 criteria and a clinical diagnosis of SSc, 83 patients with other connective tissue diseases/Raynaud\'s Phenomenon, 24 rheumatoid arthritis patients and 98 age and sex-matched healthy controls were tested for the presence of anti-CarP IgG, IgA and IgM, determined by ELISA. Clinical characteristics, that were evaluated in SSc patients, included age, anti-topoisomerase antibodies (ATA), anti-centromere antibodies (ACA) and modified Rodnan Skin Score (mRSS).
RESULTS: The SSc patients were 55 (SD:13) years and 155 (80%) were female. Forty-four (23%) patients tested positive for ATA, and 80 (42%) ACA. The median mRSS was 2 (range: 0; 47). Prevalence of anti-CarP IgG was higher in SSc patients than in healthy controls (8% vs 3%, p = 0.007. Prevalence of anti-CarP IgA and IgM and levels of anti-CarP isotypes were comparable between SSc patients and healthy controls. Fifteen (8%) SSc patients tested positive for anti-CarP IgG, 16 (8%) for anti-CarP IgA, and 36 (19%) for anti-CarP IgM. There were no significant correlations between age and levels of anti-CarP isotypes. No correlation between anti-CarP IgG levels and mRSS was found (r = 0.141, p = 0.049), nor for anti-CarP IgM and IgA levels. Anti-CarP IgA levels were higher in ATA compared to ACA positive SSc patients (ATA: 616 aU/ml [359; 1103]; ACA: 424 aU/ml [300; 673], p = 0.015).
CONCLUSIONS: SSc patients can test positive for Anti-CarP IgG, IgA and IgM. We do not observe a relevant clinical association between anti-CarP antibody response and skin involvement in SSc.

To assess the prognostic significance of skin involvement in breast cancer patients with chest wall recurrence (CWR).
We retrospectively analyzed the clinicopathological data of breast cancer patients with CWR who were diagnosed pathologically between January 2000 and April 2020. Disease-free survival (DFS) was the time from radical resection for CWR to disease recurrence. Progression-free survival (PFS) was defined as the time from the diagnosis of locally unresectable CWR to the first sign of disease progression. Persistent chest wall progression was defined as three consecutive chest wall progressions with no distant organ involvement.
A total of 476 patients with CWR were included in this study. Skin involvement was confirmed in 345 patients. Skin involvement was significantly correlated with a high T stage (p = 0.003), more positive nodes at initial examination (p < 0.001) and lymphovascular invasion (p < 0.001). Kaplan-Meier analysis showed that skin involvement was a predictor of shorter DFS (p < 0.001), including both local disease progression (p < 0.001) and distant disease progression (p = 0.022). Multivariate analysis showed that skin involvement was an independent biomarker for DFS (p = 0.043). Patients with skin involvement were more likely to experience persistent chest wall progression (p = 0.040). After eliminating the potential deviation caused by an insufficient follow-up time, persistent chest wall progression was more likely to be associated with a high N stage (p = 0.002), negative progesterone receptor (PR; p = 0.001) and positive human epidermal growth factor receptor 2 (HER2; p = 0.046) of the primary site, and negative oestrogen receptor (ER; p = 0.027) and PR (p = 0.013) of the chest wall lesion and skin involvement (p = 0.020).
Skin involvement was a predictor of poor disease control in patients with CWR and was closely related to persistent chest wall progression. We stratified the prognosis of individualized treatment for breast cancer patients with CWR to provide new insights into the biological behaviours of the disease.
Skin involvement is a predictor of poor local disease control in breast cancer patients with CWR and a factor contributing to persistent chest wall progression after CWR. We stratified the prognosis of individualized treatment for breast cancer patients with CWR.

Background Healthcare workers (HCWs) were compelled to use personal protective equipment (PPE) during the COVID-19 pandemic to prevent cross-transmission. One of the most significant challenges in responding to the COVID-19 pandemic is the consistent and effective use of PPE to avoid staff exposure and infection. This study aimed to detect and evaluate the adverse effects of PPE and determine the associated risk factors. Methodology This cross-sectional study included 186 randomly selected HCWs at Civil Hospital, Ahmedabad, from May 2022 to July 2022. An anonymous self-administered questionnaire was used for data collection, and data analysis was done using descriptive statistics. Results PPE-related adverse effects were noted among 147 HCWs, with a prevalence of 79.03%. Data analysis showed that factors significantly associated with PPE adverse effects in HCWs were age group 20-40 years (chi-squared (χ2) = 4.119, p = 0.04) and female gender (χ2 = 7.153, p = 0.007). Overall, 30.8% of participants had tested positive while on duty during the pandemic. Similarly, adverse effects were associated with PPE use of more than four hours per day and more than three days per week (χ2 = 5.477, p = 0.02 and χ2 = 6.488, p = 0.01, respectively). The majority of HCWs expressed indentation and pain on the back of the ear (52.7%) and pressure-related injury (39.8%) as adverse effects after wearing masks; skin soaking in sweat (54.83%) due to gloves; profuse sweating due to gown (64.28%); fogging (65.26%) due to googles and face-shield; and discomfort (61.29%). Conclusions The prevalence of adverse effects related to wearing PPE was alarmingly high among HCWs. The major risk factors were age, female sex, and duration of use. Although the majority of healthcare personnel have received vaccinations, the use of PPE has not altered, and severe skin reactions continue to be a global issue with no known solution. To further understand the problem, national data for the impacted healthcare professionals could be helpful. Furthermore, workplace prevention programs are necessary.

OBJECTIVE: To describe skin involvement (SI) in patients with systemic lupus erythematosus (SLE) at onset and during follow-up of the disease and to determine factors associated with SI at lupus diagnosis.
METHODS: Retrospective, observational, and descriptive study, from a single centre in patients diagnosed with SLE (ACR 1982-97 or SLICC 2012 criteria). The modified Gilliam classification for SI was used. Descriptive statistics and bivariate and multivariate analysis were performed to evaluate the factors associated with SI at diagnosis of the disease.
RESULTS: 149 patients were included, 91.3% women with a median age at diagnosis of 33 years. SI at onset of the disease occurred in 125 patients (83.9%), followed by joint involvement in 120 cases (80.5%). Non-specific skin lesions were more frequent than specific lesions, 92.8% versus 66.4%, respectively. In the bivariate analysis, a longer delay to diagnosis, the presence of joint involvement, a lower presence of thrombocytopenia, and a higher SLEDAI-2K score were associated with the presence of SI at onset of the disease. In the multivariate analysis, the variable that remained independently associated was joint involvement (OR 2.8%-95% CI 1.1-7.5, p: .04). During follow-up, 4/24 patients who had not presented SI at diagnosis and 51/125 patients who had, had at least one new skin flare (range: 1-5 outbreaks).
CONCLUSIONS: Our study demonstrates the high frequency of skin involvement in SLE, both diagnostically and evolutionarily, and confirms previously reported data regarding the existence of a skin-articular phenotype.

Inborn errors of immunity associated with atopy (IEIs-A) are a group of inherited monogenic disorders that occur with immune dysregulation and frequent skin involvement. Several pathways are involved in the pathogenesis of these conditions, including immune system defects, alterations of skin barrier and metabolism perturbations. Current technological improvements and the higher accessibility to genetic testing, recently allowed the identification of novel molecular pathways involved in IEIs-A, also informing on potential tailored therapeutic strategies. Compared to other systemic therapy for skin diseases, biologics have the less toxic and the best tolerated profile in the setting of immune dysregulation. Here, we review IEIs-A with skin involvement focusing on the tailored therapeutic approach according to their pathogenetic mechanism.

As skin involvement is the hall mark of systemic sclerosis (SSc) and changes of skin involvement have shown to correlate with internal organ involvement, assessing the extend of skin involvement is key. Although the modified Rodnan skin score is a validated tool used to evaluate the skin in SSc, it has its drawbacks. Novel imagine methods are promising but should be further evaluated. As for molecule markers for skin progression there are conflicting data on the predictive significance of baseline SSc skin gene expression profiles, but immune cell type signature in SSc skin correlates with progression.