Characteristic Skin Manifestations Research Articles

A Rare Case of Paraneoplastic Dermatomyositis in a Patient With Metastatic Endometrial Cancer

Dermatomyositis (DM) is a rare autoimmune myopathy that presents with muscle weakness and characteristic skin manifestations. Certain malignancies are associated with DM, such as stomach, colorectal, ovarian, lung, pancreatic, and non-Hodgkin lymphoma. However, there are only rare reports of endometrial cancer with DM. In this report, we describe a case of anti–TIF-1-gamma and anti-Mi-2 antibody positive DM in a patient with stage IV endometrial cancer. This case illustrates the importance of considering DM as a paraneoplastic syndrome regardless of both stage and type of malignancy.

Development of a Novel IgG1 Anaphylaxis Mouse Model with Uniquely Characteristic Skin Manifestations Induced Through the FcγRIII-Histamine Pathway

ABSTRACT Background Studies of passive anaphylaxis, in which mouse immunoglobulin G (IgG) and its antigens are administered to mice, believe that platelet-activating factor (PAF) is more important than histamine and that basophils or macrophages are primarily involved. However, the full extent of IgG-dependent anaphylaxis is still unclear; that is, little agreement has been reached about the mechanism. Methods First, we established the novel model of IgG1 anaphylaxis induced by the intravenous administration of two types of IgG1 and a fluorescent dye-labeled antigen, as IgG1 immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG1 anaphylaxis in this established model. Results The novel IgG1 anaphylaxis model can induce the IgG-induced Anaphylaxis-dependent Spotted Distribution of fluorescently labeled Immune complexes in the Skin, named “G-ASDIS”. Moreover, this model was triggered primarily by the FcγRIII-dependent histamine release, which is different from the conventional model in which PAF was involved in the development of IgG1 anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG1 anaphylaxis and increased G-ASDIS. Conclusion Our results propose that the novel axis, namely the FcγRIII-basophils and/or mast cell-histamine pathway, is important for IgG1 anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG1 anaphylaxis mechanism.

Interstitial lung disease is a dominant feature in patients with circulating myositis-specific antibodies

BackgroundMany patients with polymyositis (PM) or dermatomyositis (DM) have circulating myositis-specific antibodies (MSAs). Interstitial lung disease (ILD) is a common manifestation of PM/DM, and it can even precede the onset of characteristic muscle or skin manifestations. Furthermore, there appear to be some patients with ILD and circulating MSAs who do not develop muscle or skin disease even after prolonged follow-up. We sought to determine whether ILD is equally or more common than myositis or dermatitis at the time of initial detection of MSAs.MethodsWe identified all patients found to have circulating MSAs at our institution over a 4-year period and assessed for the presence of lung, muscle, and skin disease at the time of initial detection of MSAs. Among those found to have ILD, we compared demographic and clinical features, chest CT scan findings, and outcomes between those with PM/DM-associated ILD and those with ILD but no muscle or skin disease.ResultsA total of 3078 patients were tested for MSAs, and of these 40 were positive. Nine different MSAs were detected, with anti-histidyl tRNA synthetase (anti-Jo-1) being the most common (35% of MSAs). Among patients with positive MSAs, 86% were found to have ILD, compared to 39% and 28% with muscle and skin involvement, respectively (p < 0.001). Fifty percent of all MSA-positive patients had isolated ILD, with no evidence of muscle or skin disease. Those with isolated ILD were more likely to be older and have fibrotic changes on chest CT, less likely to receive immunomodulatory therapy, and had worse overall survival.ConclusionsIn this study we found that individuals with circulating MSAs were more likely to have ILD than classic muscle or skin manifestations of PM/DM at the time of initial detection of MSAs. Our findings suggest that the presence of ILD should be considered a disease-defining manifestation in the presence of MSAs and incorporated into classification criteria for PM/DM.

Follicular Occlusion Triad: A Case Report

Follicular occlusion triad (FOT) is a complex chronic inflammatory skin disease comprising hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS; Hoffman’s disease or perifolliculitis capitis abscedens et suffodiens). While pathological mechanisms are responsible for common skin manifestations, the exact underlying causes of follicular occlusion have not yet been clearly identified. Therefore, the diagnosis and treatment of FOT remain challenging. A 31-year-old man on conservative treatment for previously diagnosed HS and AC presented to our clinic with multiple masses on his posterior neck and face. Excisional biopsy of the masses revealed epidermal cysts. Four months after the surgery, he presented with a painful palpable mass around the occipital region of the scalp with characteristic skin manifestations such as cicatricial alopecia and comedones and was diagnosed with DCS. Incision and drainage of the lesion were performed, and histopathology revealed pathological findings of follicular occlusion. The patient was diagnosed with FOT. Following the procedure, the patient has been on regular follow-up and is on oral isotretinoin; there have been no complications for the last 6 months.

Expert-Level Distinction of Systemic Sclerosis from Hand Photographs Using Deep Convolutional Neural Networks

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic autoimmunity and tissue fibrosis of the skin and internal organs (Medsger, 2003). Early clinical interventions for SSc lead to early detection of complications, resulting in improved patient prognosis (Denton and Khanna, 2017). Therefore, early diagnosis of SSc is important. SSc presents with characteristic skin manifestations such as Raynaud’s phenomenon and skin sclerosis from early onset (Gunnarsson et al., 2016; LeRoy, 1992).

Skin Manifestations in Dermatomyositis and Antisynthetase Syndrome

Dermatomyositis and antisynthetase syndrome are among idiopathic inflammatory myopathies (myositis) that have skin lesions. In these disorders, skin symptoms often appear as the initial manifestations, and thus, their evaluation is critical for diagnosis. Two components, "site" and "properties," are important for understanding the skin manifestations in myositis. The rash in these disorders is induced by Koebner's phenomenon, and is most frequently observed on the hands and face. Recent studies have shown that myositis-specific autoantibodies are useful tools for the diagnosis and classification of these diseases, as they are closely correlated with the clinical and histopathological phenotypes of myositis. It has recently become clear that each antibody is associated with characteristic skin manifestations, especially related to the properties of the skin lesions.

Dermatomyositis syndrome in small cell lung cancer

Dermatomyositis is a progressive systemic disease clinically manifested by a muscle lesion with impaired motor function as well as skin rashes, often in the form of erythema. In some cases, dermatomyositis can be the onset of cancer. In this regard, the doctor is required to be highly alert and focused on detecting the tumor process in patients with progressive muscle weakness and characteristic skin manifestations of dermatomyositis. The article presents a clinical case of paraneoplastic dermatomyositis co‐existing with small cell lung cancer. The malignancy was diagnosed during cancer screening in a patient with classic manifestations of dermatomyositis. Improvement of clinical manifestations of dermatomyositis appeared with glucocorticosteroid therapy and surgical treatment, but the patient died, since small cell lung cancer has an aggressive clinical course with an unfavorable prognosis.

AUTOIMMUNE MYOPATHIES: P.296 The ProDERM study: A randomized, double-blinded, placebo controlled trial of IVIG (Octagam 10%) in patients with dermatomyositis

Dermatomyositis (DM) is a rare chronic autoimmune condition with characteristic skin manifestations and progressive proximal muscle weakness. Although treatments such as glucocorticoids and other immunosuppressive or immunomodulatory therapies including immunoglobulins are used, evidence supporting their efficacy in DM is limited. The ProDERM study aimed to investigate the efficacy and safety/tolerability of intravenous immunoglobulins (IVIG - Octagam 10%) in patients with DM in a prospective, parallel group, double-blind, randomized, placebo-controlled, international multicenter, phase III study.

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review

Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin manifestations, such as edema, erythema, induration, peau d'orange appearance, and the groove sign, are of diagnostic significance and observed in the majority of patients with EF. We herein report a case of EF without these characteristic skin manifestations. A 66-year-old Japanese woman developed progressive limb pain and motor dysfunction. No skin changes were observed. We diagnosed the patient with EF based on the clinical course, magnetic resonance imaging, and en bloc biopsy containing fascia and muscle. Oral prednisolone therapy markedly attenuated limb pain and motor dysfunctions. Through a systemic search of the medical literature, we retrieved 4 juvenile cases and 8 adult cases of EF without characteristic skin manifestations during the clinical course. We herein present a systemic review on EF without skin manifestations and discuss differences between the two proposed sets of diagnostic criteria of EF.

COVID-19 Usurps Host Regulatory Networks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the cell surface and this complex is internalized. ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS). Understanding the pathophysiological effects of SARS-CoV-2 on these pathways is needed, particularly given the current lack of proven, effective treatments. The vasoconstrictive, prothrombotic and pro-inflammatory conditions induced by SARS-CoV-2 can be ascribed, at least in part, to the activation of these intersecting physiological networks. Moreover, patients with immune deficiencies, hypertension, diabetes, coronary heart disease, and kidney disease often have altered activation of these pathways, either due to underlying disease or to medications, and may be more susceptible to SARS-CoV-2 infection. Certain characteristic COVID-associated skin, sensory, and central nervous system manifestations may also be linked to viral activation of the RAAS, complement, coagulation, and KKS pathways. Pharmacological interventions that target molecules along these pathways may be useful in mitigating symptoms and preventing organ or tissue damage. While effective anti-viral therapies are critically needed, further study of these pathways may identify effective adjunctive treatments and patients most likely to benefit.

Skin manifestations in spondyloarthritis.

Spondyloarthritides (SpA) like psoriatic arthritis, axial spondyloarthritis/ankylosing spondylitis, reactive arthritis and inflammatory bowel disease (IBD)-associated SpA can present with characteristic skin manifestations. These SpA-associated skin disorders may precede joint involvement, reflect a loss of efficacy of a current systemic treatment or can even be treatment associated. Cutaneous manifestations in SpA not only add additional morbidity with physical impact but also impose a psychosocial burden on affected patients. Psoriasis (PsO) – the main skin disease in SpA – has a variety of clinical presentations, including plaque-type PsO, inverse PsO, guttate PsO, erythrodermic PsO, nail PsO and pustular types. SpA associated with IBD presents with neutrophilic and granulomatous skin disorders, including pyoderma gangrenosum, hidradenitis suppurativa and cutaneous Crohn’s disease. Reactive arthritides has a favourable prognosis and may feature keratoderma blenorrhagicum or balanitis circinatum as typical skin manifestations. Immunologically, SpA-associated skin diseases share interleukin (IL)-17 and IL-23 dysregulation but show distinctive genetic and immunological profiles. Therefore, they vary in their treatment responses to targeted therapies with biologicals or small molecules. In this review, we highlight the clinical presentation of skin manifestations in SpA and discuss therapeutic approaches in this interdisciplinary field.

Cutaneous manifestations of dermatomyositis characterized by myositis-specific autoantibodies.

Dermatomyositis (DM) is an inflammatory myopathy with characteristic skin manifestations, the pathologies of which are considered autoimmune diseases. DM is a heterogeneous disorder with various phenotypes, including myositis, dermatitis, and interstitial lung disease (ILD). Recently identified myositis-specific autoantibodies have been associated with distinct clinical features. For example, anti-melanoma differentiation-associated protein 5 antibodies have a high specificity for clinically amyopathic DM presenting rapidly progressive ILD. Furthermore, anti-transcriptional intermediary factor 1γ antibodies found in patients with juvenile and adult DM are closely correlated with malignancies, especially in elderly patients. Finally, patients with anti-aminoacyl-transfer RNA synthetase antibodies share characteristic clinical symptoms, including myositis, ILD, arthritis/arthralgia, Raynaud’s phenomenon, and fever; thus, the term “anti-synthetase syndrome” is also used. With a focus on the characteristic cutaneous manifestations in each subgroup classified according to myositis-specific autoantibodies, we introduce the findings of previous reports, including our recent analysis indicating that skin eruptions can be histopathologically classified into myositis-specific autoantibody-associated subgroups and used to determine the systemic pathologies of the different types of antibody-associated DM.

Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease.

Anti-melanoma differentiation-associated gene5 (MDA5) antibody has been recognized to be significantly associated with a subset of dermatomyositis patients with rapidly progressive interstitial lung disease (RP-ILD). To elucidate the clinical characteristics and poor prognostic factors in Japanese dermatomyositis patients with anti-MDA5 antibody. Clinical features of anti-MDA5 antibody-positive dermatomyositis patients and risk factors, potentially associated with a poor prognosis, were retrospectively analysed. A total of 37.3% (28/75) dermatomyositis patients were positive for anti-MDA5 antibody. The frequency of Gottron's papules, palmar violaceous macules, antihelix/helix violaceous macules, and clinically amyopathic dermatomyositis (CADM) was significantly higher in patients with anti-MDA5 antibody. Of anti-MDA5 antibody-positive dermatomyositis patients, 57.1% developed RP-ILD, and in those with RP-ILD, serum ferritin level was markedly high and partial pressure of arterial oxygen (PaO2) was significantly low at first visit. Among patients with anti-MDA5 antibody with RP-ILD, non-survivors were older and revealed lower PaO2 at first visit relative to survivors. Furthermore, patients who did not take triple therapy (prednisolone, calcineurin inhibitor and cyclophosphamide) as initial treatment resulted in poor outcome. Anti-MDA5 antibody may be associated with CADM, the progression to RP-ILD, high serum ferritin level, and characteristic skin manifestations. High serum ferritin level in patients with anti-MDA5 antibody may be associated with the development of RP-ILD and poor prognosis. Early treatment with triple therapy, including intravenous cyclophosphamide, may improve the prognosis of RP-ILD.

Meeting the Challenges of the Dermatomyositis Workup: A Management Paradigm

Dermatomyositis (DM) is a rare inflammatory myopathy with characteristic skin manifestations. This multisystem disorder is characterized by an increased frequency of pulmonary disease and malignancy. It has a female to male predominance of 2:1, with an average age at diagnosis of 40 years [1]. Diagnosing DM can be challenging due to the heterogeneity of presentations and clinical features that may overlap with other disorders. Although DM has had an established diagnostic criteria by Bohan and Peter since 1975, groups have re-examined the criteria to highlight the importance of skin findings [2-4]. This article will discuss the process of working-up dermatomyositis in an adult from a dermatologist’s point of view.

Netherton Syndrome: A Case Report and Review of Literature

Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by a triad of congenital ichthyosiform erythroderma (CIE) or ichthyosis linearis circumflexa (ILC), hair shaft abnormalities, and atopic diathesis (elevated serum IgE ). We report a case of a two-year-old boy presented with intractable pruritus, scaling, dry skin and generalized eczematous lesions resistant to atopic dermatitis therapy. Netherton syndrome misdiagnosed as atopic dermatitis due to the presence of eczematous skin lesions and allergic problems. The family counseled about the diagnosis and need of genetic testing for confirmation, but they refused for genetic testing. The patient got treatment with topical corticosteroids and skin moisturizers. There is no cure or satisfactory treatment currently available for NS. Further understanding of the underlying pathophysiology of integumentary changes will lead to more effective treatment. Netherton syndrome should be in the differential diagnosis when characteristic skin manifestation of CIE or ILC, and elevated serum IgE present.

Antibodies to small ubiquitin-like modifier activating enzyme are associated with a diagnosis of dermatomyositis: results from an unselected cohort.

The aim of this study was to examine the frequency and significance of antibodies targeting the small ubiquitin-like modifier 1 activating enzyme (SAE) in patients under serologic evaluation for idiopathic inflammatory myopathies. Patient sera (n = 17) recognizing bands at approximately 40 (SAE1) and 90 (SAE2) kDa were identified in 6445 consecutive samples for myositis autoantibody evaluation by immunoprecipitation (IP) of S35-labeled K562 cell lysate. All 17 positive samples, 176 disease, and 67 healthy controls were evaluated for SAE1 antibodies using a line immunoblot assay (LIA). Clinical data of SAE antibody-positive patients were obtained by retrospective chart review. Positivity with both methods was associated with a diagnosis dermatomyositis with characteristic skin manifestations of varying severity and muscle involvement. Majority of the patients were female (73.7%), mean age of 55.0 (range 12.0-82.0) years at the time of testing. Using the IP as reference, the SAE1 LIA had a sensitivity of 100% (95% CI 82.4-100%), specificity of 99.6% (95% CI 97.7-100%), positive predictive value of 95.0% (95% CI 75.1-99.9%), and negative predictive value of 100% (95% CI 98.5-100%). This study confirms the association of SAE antibodies in patients with dermatomyositis. A combination of IP and the LIA specific for SAE1 may be useful in antibody detection.

Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion

A 68-year-old woman was admitted to our hospital with fever and pleural effusion. Her thoracentesis showed eosinophilic pleural effusion (EPE) without any evidence of malignancy, infection, or trauma. Pleural biopsy revealed pleuritis and intercostal myositis. Characteristic skin manifestations, including Gottron's sign, interstitial lung disease, and pericardial effusion, appeared later in the clinical course. She was finally diagnosed with anti-PL-7 antisynthetase syndrome (ASS) based on the presence of anti-PL-7 antibody, and she fulfilled the diagnostic criteria for dermatomyositis. These clinical manifestations improved with immunosuppressive therapy. EPE might therefore be one of the characteristic features of anti-PL-7 ASS.

Diagnosis and Management of Conjunctivitis for the Dermatologist.

Atopic dermatitis is a chronic, sometimes relapsing inflammatory skin condition that presents with pruritus and characteristic skin manifestations. Conjunctivitis is a common ocular comorbidity affecting almost half of patients with the risk increasing with atopic dermatitis severity. Recent targeted biologic therapies that successfully treat atopic skin disease, including dupilumab, which blocks interleukin (IL)-4 and IL-13, as well as agents that block IL-13 alone, have been associated with an increased rate of conjunctivitis in clinical trials. Because conjunctivitis commonly occurs in patients with atopic dermatitis and as the treatment with targeted biologic agents may increase the risk or severity of conjunctivitis, it is important that dermatologists recognize symptoms, appreciate treatment options, and know when referral to an ophthalmologist is appropriate.

Current state of yusho and prospects for therapeutic strategies.

The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients. Lipophilic dioxins are retained in the body for a longer period than previously estimated. Victims suffered from characteristic skin manifestations associated with non-specific systemic symptoms, neurological symptoms, and respiratory symptoms. The severe symptoms seen in the initial phase subsequently faded, but recently, improvements have scarcely been observed. The Yusho Group has been researching treatments for this condition. Several clinical trials with chelating agents or dietary fibers aimed at accelerating the excretion of compounds. While some treatments increased dioxin excretion, none provided satisfactory symptom relief. Concurrently, various phytochemicals and herbal extracts have been found to possess biological activities that suppress dioxin-induced toxicity via aryl hydrocarbon receptor or activate the antioxidant nuclear factor-erythroid 2-related factor-2 (NRF2) signal pathway, making them promising therapeutic candidates. Here, we summarize the current status of yusho and findings of clinical trials for yusho patients and discuss the treatment prospects.

Lyme Disease: Emergency Department Considerations

BackgroundLyme disease (LD) is the most common vector-borne illness in North America. Reported cases of LD have increased from approximately 10,000 cases annually in 1991 to >25,000 cases in 2014. Greater recognition, enhanced surveillance, and public education have contributed to the increased prevalence, as have geographic expansion and the number of infected ticks. Cases are reported primarily in the Northeastern United States, Wisconsin, and Minnesota, with children having the highest incidence of LD among all age groups. The increased incidence and prevalence of LD in the United States makes it increasingly more common for patients to present to the emergency department (ED) for tick bites and LD-related chief complaints, such as the characteristic erythema migrans skin manifestation. ObjectiveWe sought to review the etiology of LD, describe its clinical presentations and sequela, and provide a practical classification and approach to ED management of patients with LD-related presentations. DiscussionIn this review, ED considerations for LD are presented and clinical presentations and management of the disease at different stages is discussed. Delayed sequelae that have significant morbidity, including Lyme carditis and Lyme neuroborreliosis, are discussed. Diagnostic tests and management are described in detail. ConclusionThe increasing prevalence and growing geographic reach of Lyme disease makes it critically important for emergency physicians to consider the diagnosis in patients presenting with symptoms suggestive of LD and to initiate appropriate treatment to minimize the potential of delayed sequelae. Special consideration should be made for the epidemiology of LD and a high clinical suspicion should be present for patients in endemic areas or with known exposures to ticks. Emergency physicians can play a critical role in the recognition, diagnosis, and treatment of LD.