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Background and 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. Conclusion: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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). Conclusion 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.

AbstractPurpose To assess the prognostic significance of skin involvement in breast cancer patients with chest wall recurrence (CWR).Methods 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.Results 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

Describir el compromiso cutáneo (CC) en pacientes con lupus eritematoso sistémico (LES) al inicio de la enfermedad y durante el seguimiento. Determinar factores asociados a dicho compromiso al comienzo de la enfermedad. Estudio retrospectivo, observacional y descriptivo, de centro único, en pacientes con diagnóstico de LES (ACR 97 o SLICC 2012). Se utilizó la clasificación de Gilliam modificada para el CC. Se realizó estadística descriptiva y análisis bivariado y multivariado para evaluar los factores asociados al compromiso cutáneo. Se incluyeron 149 pacientes (91,3% mujeres) con una mediana de edad al diagnóstico de 33 años. El CC al inicio de la enfermedad ocurrió en 125 pacientes (83,9%), seguido por compromiso articular en 120 (80,5%). Las lesiones no específicas fueron más frecuentes que las específicas: 92,8% versus 66,4%, respectivamente. En el análisis bivariado, la mayor demora al diagnóstico, la presencia de compromiso articular, la menor presencia de trombocitopenia y la mayor puntuación de SLEDAI-2K se asociaron con la presencia de CC al inicio de la enfermedad. En el análisis multivariado, la variable que se mantuvo asociada de manera independiente fue el compromiso articular (OR: 2,8; IC 95%: 1,1-7,5; p = 0,04). Durante el seguimiento, 4/24 pacientes que no habían presentado CC al diagnóstico y 51/125 pacientes que sí lo presentaron tuvieron al menos un nuevo episodio cutáneo (rango: 1-5 brotes). Nuestro estudio demuestra la alta frecuencia de pacientes que presentan compromiso cutáneo en el LES, tanto en el diagnóstico como evolutivamente, y confirma los datos reportados previamente en cuanto a la existencia de un fenotipo cutáneo-articular. 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. 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. A total of 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). 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. [ABSTRACT FROM AUTHOR]

Male breast cancer is a rare disease with an unknown etiopathogenesis. We report a case of a 50-year-old man with a breast cancer revealed by skin involvement.

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.

Chronic myelomonocytic leukemia is a clonal hematopoietic stem cell disorder with both myelodysplastic and myeloproliferative features, leading to a variable clinical presentation. Some types of skin involvement, such as leukemia cutis and blastic plasmacytoid dendritic cell neoplasia, are associated with poor prognosis. This case study describes a 71-year-old male with high-risk CMML, developing pink-purple skin nodules, which regressed with azacitidine and hydroxyurea treatment. Despite recurrence, disease control was achieved without transformation to acute leukemia. This case highlights the need for vigilant monitoring and adaptable treatment strategies in managing CMML with skin involvement., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arslan Davulcu et al.)

The article presents a case study of a 02-year-old boy with pediatric nephrology outpatient clinic due to nephrotic range proteinuria. Topics include skin biopsy revealing compact orthokeratosis in the epidermis, occasional subepidermal separation foci, and hydropic degeneration in the basal layer; and prednisolone being used in the treatment of nephrotic syndrome.

The article presents the discussion on nephrotic syndrome, skin involvement, and chronic lung disease. Topics include diagnostic approach to the steroid-resistant nephrotic syndrome in children with extrarenal fndings; and light microscopy of the biopsy showing focal segmental glomerulosclerosis, mononuclear cell infltration .

BackgroundSystemic lupus erythematosus (SLE) can significantly influence patients’ quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied.ObjectiveTo measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB.MethodsOverall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB.ResultsLife satisfaction was significantly lower (p < 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868–0.981, p < 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092–1.230, p < 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022–1.153, p < 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004–1.133, p < 0.05).ConclusionSWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.

Purpose: MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods: The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. Results: The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). Conclusion: This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life. [ABSTRACT FROM AUTHOR]

Background: Cutaneous involvement by classic Hodgkin lymphoma (CHL) is an extraordinarily rare phenomenon in the current era. To date, no single large case series of cutaneous involvement by Hodgkin lymphoma has ever been reported in the literature. Methods: A comprehensive search for cases designated "skin" and "Hodgkin" was performed at different institutions between 1990 and 2020. Twenty‐five cases were identified, and each case was independently reviewed by at least three board‐certified dermatopathologists and/or hematopathologists. Results: All cases represented examples of systemic CHL with secondary skin dissemination. A single lesion, usually a tumor, nodule or infiltrative plaque was observed in 56% of cases and multiple lesions were present in 28% of cases. Most patients (86%—12/14) had a diagnosis of stage IV disease at first diagnosis. The interval between the clinical (first) diagnosis of HL and the development of skin lesions ranged between 6 and 108 months (average 33.75 months). Comprehensive histopathologic evaluation of these cases (at the initial diagnosis) revealed a diagnosis of classic HL not otherwise specified (NOS) in 60% of cases (15/25), nodular sclerosis type in 24% (6/25), mixed cellularity in 12% (3/25), and lymphocyte depleted in 4% (1/25). Conclusions: We provide documentation of a large series of CHL with secondary skin involvement in association with CHL with additional clinical, morphologic, and immunophenotypic features. [ABSTRACT FROM AUTHOR]

Mastocytosis is a rare clonal disorder, characterized by excessive proliferation and accumulation of mast cells (MC) in various organs and tissues. Cutaneous mastocytosis (CM), the most common form in children, is defined when MC infiltration is limited to the skin. Systemic mastocytosis (SM), the most common form in adults, is characterized by MC proliferation and accumulation in organs, such as bone marrow, lymph nodes, liver and spleen (1). Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis, resulting in enhancing MC survival and subsequent accumulation in organs and tissues (2,3). CM includes 3 forms: solitary mastocytoma, maculopapular cutaneous mastocytosis (MPCM) and diffuse cutaneous mastocytosis (DCM). In the majority of children with CM, skin lesions regress spontaneously around puberty; unfortunately, in a few cases, it is not a self-limiting disease (4). Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. Children with mastocytosis often suffer from MC mediator-related symptoms, the most common of which is itching, often triggered by rubbing the lesions. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers. Treatment with H1 and H2 histamine receptor blockers on demand, and the availability of epinephrine auto-injectors for the patients to use in case of severe anaphylactic reactions are recommended.

Objective: To assess the oncological outcome and prognostic factors for primary Oral Squamous Cell Cancer (OSCC) staged as per AJCC 8th pTNM, and treated by the contemporary standard of primary surgery and pathology directed adjuvant radiation-chemoradiation.Methods: A single institution cohort from a tertiary care academic institution in North India. Case inclusion 2013 to 2016; n = 218, median follow-up 35 months. All patients were restaged as per the AJCC 8th pTNM classification. Analysis for Overall Survival (OS), Disease-free Survival(DFS), and factors impacting outcome (Cox proportionate model Multivariate analysis).Results: AJCC pTNM 7th to 8th edition conversion led to upstaging in 16.5%. Stage-II demonstrated greatest stage migration and apparent improvement in OS and DFS (P < .09). Discordance was noted between the presurgical (clinico-radiologic) and postsurgical (pathological) nodal status in 40.3% (88/218; 54 pathologically upstaged;34 downstaged). Pathological downstaging was particularly significant with advanced stage Gingivo-Buccal Cancers (25/73-34.7%). Stage-I-II early cancers had 3 years. OS-86.7% and DFS-78.8%; Stage-III-IV advanced cancers had 3 years. OS-56.7% and DFS-46.6%. Multivariate analysis identified poorer OS and DFS for age < 40 years (HR-1.8; 2.0), skin involvement (HR-2.1; 2.6) and pN+ status (HR-2.4; 3.5). Bone involvement did not compromise survival in this surgically treated set of patients.Conclusion: Age < 45 is newly identified as significantly compromising DFS and OS in Oral Cancer. Established factors of skin involvement and pN+ are confirmed as impacting DFS-OS. An apparent improvement in survival in Stage II Cancers is noted as consequent to adoption of AJCC 8th edition staging.Level Of Evidence: 2 (OCEBM 2011-Inception Cohort Study for Prognosis) Laryngoscope, 131:2254-2261, 2021. [ABSTRACT FROM AUTHOR]

Summary: Cutaneous metastatic Crohn's disease (MCD) is a rare but challenging dermatologic manifestation of Crohn's disease. It is histologically defined as the presence of non‐caseating granulomas at skin sites separated from and non‐contiguous to the gastrointestinal tract. Cutaneous metastatic Crohn's disease should be distinguished from the much more frequent contiguous cutaneous manifestations of Crohn's disease that present at perianal or, less common, peristomal sites with direct extension from the intestine to the adjacent skin. Versatile clinical presentation and the fact that occurrence can predate the initial diagnosis of Crohn's disease may lead to misdiagnosis, delayed treatment and underreporting. As case numbers are small and randomized controlled studies on management are lacking, the therapeutic approach remains challenging and is often unsatisfactory. We here performed a systematic literature search identifying 264 published pediatric and adult cases of MCD and additionally report three of our own cases. Our review summarizes clinical characteristics, putative etiopathology, histologic findings, differential diagnoses and treatment options for MCD. [ABSTRACT FROM AUTHOR]

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ.What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases.What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a “Cultured melanocyte elongation and proliferation (CMEP)” factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory.

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a "Cultured melanocyte elongation and proliferation (CMEP)" factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to investigate the frequency and the distribution of inflammatory cell infiltrate in two sets of cutaneous biopsies derived from clinically affected and unaffected skin in patients with systemic sclerosis (SSc) and to test correlation between the cell infiltrate and the progression of skin involvement. Methods Skin was immunohistochemically assessed to identify CD68, CD3, CD20 and CD138-positive (+) cells in clinically affected and unaffected skin in 28 patients with SSc. Patients were followed for 6 months and the characteristics of the infiltrate were analyzed according to disease duration, clinical features and skin involvement progression. Results In all SSc cutaneous specimens, cellular infiltrates were found in a perivascular location predominantly in the mid and deeper portions of the dermis. All the analyzed biopsies showed a CD3+ and CD68+ cell infiltrate and the mean number of CD3+ and of CD68+ cells was higher in clinically involved skin (CD3+, 71.7 ± 34.6 and CD68+, 26.3 ± 8.4, respectively) than in clinically uninvolved skin (CD3+, 45.7 ± 36.0 and CD68+, 13.6 ± 6.1, respectively) (p

Mastocytosis is a rare clonal disorder characterized by excessive proliferation and accumulation of mast cells (MC) in various organs and tissues. Cutaneous mastocytosis (CM), the most common form in children, is defined when MC infiltration is limited to the skin. In adults, the most common form is systemic mastocytosis (SM), characterized by MC proliferation and accumulation in organs, such as bone marrow, lymph nodes, liver, and spleen.1 Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis, enhancing MC survival and subsequent accumulation in organs and tissues.2,3 CM includes three forms: solitary mastocytoma, maculopapular cutaneous mastocytosis (MPCM), and diffuse cutaneous mastocytosis (DCM). In most children with CM, skin lesions regress spontaneously around puberty; unfortunately, it is not always a self-limiting disease.4 Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. Children with mastocytosis often suffer from MC mediator-related symptoms, the most common of which is itching, often triggered by rubbing the lesions. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers. Treatment with H1 and H2 histamine receptor blockers on demand and the availability of epinephrine auto-injectors for the patients to use in case of severe anaphylactic reactions are recommended. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic granulomatous disease of unknown cause. Skin involvement may be specific lesions in which granulomas are detected on biopsy or nonspecific lesions without granulomatous inflammation on biopsy. Lupus pernio (LP) occurs in the form of smooth, bright nodules and plaques on the nose, ear, lips, and cheeks. Although presence of skin involvement is frequent, lupus perio is reported as a rare form of extrapulmonary sarcoidosis. A 57-year-old female patient applied to the dermatology outpatient clinic with a lesion on the nose. We report a case of chronic sarcoidosis presenting with lupus pernio with clinical and radiological improvement. [ABSTRACT FROM AUTHOR]

Objective High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls. Methods Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis. Results UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P < 0.05), while in the forearm it was significantly lower in patients than in controls (P < 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve >0.7). Conclusion These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects. [ABSTRACT FROM AUTHOR]

Secondary scrotal tumors originating from viscera are rare and indicate a poor prognosis. We report a patient who underwent abdominoperineal resection due to his rectal cancer. Tumor recurrence at the surgical site led to prostate involvement. About 1 month after the prostatectomy, scrotal skin metastasis presented as bilateral papulonodular lesions. Finally, brain metastasis occurred and caused his death. Also, several ways by which malignancies can metastasize to scrotum have been discussed.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving the skin and internal organs and characterized pathologically by microvascular damage and increased deposition of connective tissue. Skin changes seen in SSc include edema, inflammation, induration, thickening, and progressive skin fibrosis. Histologically, skin fibrosis, accumulation of compact collagen in the dermis, effacement of rete pegs, infiltration by CD4+ T cells, and skin atrophy are observed. The “toxic oil syndrome” reported from Spain caused an outbreak of a scleroderma-like illness and was caused by ingestion of contaminated rapeseed cooking oil. Epidemic dropsy is caused by ingestion of mustard oil contaminated with the oil of Argemone mexicana. The major alkaloids in Argemone oil are sanguinarine and dihydrosanguinarine. These alkaloids produce widespread capillary dilatation, increased capillary permeability, and endothelial proliferation, akin to the toxic oil syndrome. Cutaneous manifestations include erythematous and tender bilaterally symmetrical pitting edema usually involving lower limbs, skin thickening and tethering, pigmentation, and presence of telangiectasias. The dermatopathology observed in epidemic dropsy includes atrophy and flattening of rete pegs, hypertrophy of and deposition of collagen, vascular dilatation and proliferation, and subcutaneous inflammation and fibrosis. Epidemic dropsy usually presents with subacute multisystem involvement, which may mimic a connective tissue disease. Skin involvement in epidemic dropsy may closely mimic cutaneous manifestations in SSc, both clinically and histologically. Thus, the clinician needs to be aware that epidemic dropsy with cutaneous involvement, especially if encountered sporadically, may be mistakenly diagnosed as scleroderma.

Brucellosis is a zoonotic disease that is common all over the world. Although musculoskeletal involvement is common in the course of the disease, skin rash is very rare. Newly examined and observed papulopustular skin rash has not been reported before. In this study, a case of acute brucellosis is presented with fever, septic arthritis, and papulopustular rash. The diagnosis of brucellosis was made by serological tests. The patient was treated with doxycycline 100 mg twice a day, rifampicin 600 mg daily, and gentamicin 320 mg daily. Clinicians should be aware of brucellosis in the differential diagnosis of patients presenting with rash or septic arthritis in endemic areas. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving the skin and internal organs and characterized pathologically by microvascular damage and increased deposition of connective tissue. Skin changes seen in SSc include edema, inflammation, induration, thickening, and progressive skin fibrosis. Histologically, skin fibrosis, accumulation of compact collagen in the dermis, effacement of rete pegs, infiltration by CD4+ T cells, and skin atrophy are observed. The "toxic oil syndrome" reported from Spain caused an outbreak of a scleroderma-like illness and was caused by ingestion of contaminated rapeseed cooking oil. Epidemic dropsy is caused by ingestion of mustard oil contaminated with the oil of Argemone mexicana. The major alkaloids in Argemone oil are sanguinarine and dihydrosanguinarine. These alkaloids produce widespread capillary dilatation, increased capillary permeability, and endothelial proliferation, akin to the toxic oil syndrome. Cutaneous manifestations include erythematous and tender bilaterally symmetrical pitting edema usually involving lower limbs, skin thickening and tethering, pigmentation, and presence of telangiectasias. The dermatopathology observed in epidemic dropsy includes atrophy and flattening of rete pegs, hypertrophy of and deposition of collagen, vascular dilatation and proliferation, and subcutaneous inflammation and fibrosis. Epidemic dropsy usually presents with subacute multisystem involvement, which may mimic a connective tissue disease. Skin involvement in epidemic dropsy may closely mimic cutaneous manifestations in SSc, both clinically and histologically. Thus, the clinician needs to be aware that epidemic dropsy with cutaneous involvement, especially if encountered sporadically, may be mistakenly diagnosed as scleroderma. [ABSTRACT FROM AUTHOR]

Skin involvement in SSc is an important marker of disease activity, severity and prognosis, making the assessment of skin a key issue in SSc clinical research. We reviewed the published data assessing skin involvement in clinical trials and summarized the major conclusions important in SSc clinical research. A systematic literature review identified randomized controlled trials using skin outcomes in SSc. Analysis examined the validity of the different skin measures based on literature findings. Twenty-two randomized controlled trials were found. The average study duration was 10.2 (S.D. 4.5) months, mean (S.D.) sample size 32.4 (32.6) and 26.7 (27.8) in intervention and control arms, respectively. The 17-site modified Rodnan skin score is a fully validated primary outcome measure in diffuse cutaneous SSc. Skin histology seems to be an appropriate method for evaluation of skin thickness. These findings have important implications for clinical trial design targeting skin involvement in SSc. [ABSTRACT FROM AUTHOR]

Summary Cryptococcosis is a potentially fatal fungal disease caused by the basidiomycetes yeasts Cryptococcus neoformans and C. gattii with high predilection to invade the central nervous system mainly in immunocompromised hosts. Skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation with contaminated materials. We report the first two Libyan cases of cryptococcal meningitis in HIV patients, in which one of them presented a secondary cutaneous involvement due to systemic dissemination. The first patient was a 17-year-old female, had fever, cough, headache and intractable vomiting as well as itchy water bumps on her skin and upper limbs. The cutaneous eruption prompted the accurate diagnosis. Cultures were positive for C. neoformans in both cerebrospinal fluid and skin specimens, as well as cryptococcal antigen was detected in serum. The isolate was identified, by molecular analysis, as C. neoformans AD-hybrid belonging to molecular type VNIII and mating type αAAα, the same genotype found for some environmental isolates recovered from olive trees in Tripoli. The second patient was a 36-years-old male with a long history of HIV on irregular treatment. Cryptococcal antigen in serum was positive and cultures yielded the growth of C. neoformans var. grubii , molecular type VNI and mating type αA. Both patients did not respond adequately to treatment and died of impaired central nervous system function and respiratory failure, respectively. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that commonly affects extranodal sites. The most commonly affected sites are the bone marrow, gastrointestinal tract, Waldeyer's ring, lung, and pleura. We report the case of an 80-year-old diabetic male, in MCL remission, who presented with a small dome-shaped nodule on his calf and an ipsilateral second digit non-healing ulceration after a traumatic fall. Despite surgical and conservative treatment, the wound worsened, resulting in histopathologic examination, which confirmed the presence of lymphocytes, indicating MCL relapse. This case was followed up for approximately 3 months until the patient died. Our case is an example of pedal manifestations of skin involvement of MCL, which, on consideration of the clinical manifestations also, can be confused with a nonhealing diabetic wound. The clinical significance of our case study is to assist in the diagnosis, management, and prognosis of a patient with MCL. [ABSTRACT FROM AUTHOR]

Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4-year history of indolent WM developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations. [ABSTRACT FROM AUTHOR]