Generalized Pustular Psoriasis and Systemic Organ Dysfunctions.

This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies.

Maresin-1 and Inflammatory Disease.

Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction sometimes exceeds tissue damage and can disrupt organ functions. Therefore, anti-inflammatory action and resolution mechanisms need to be clarified. Dietary foods are an essential daily lifestyle that influences various human physiological processes and pathological conditions. Especially, omega-3 fatty acids in the diet ameliorate chronic inflammatory skin diseases. Recent studies have identified that omega-3 fatty acid derivatives, such as the resolvin series, showed strong anti-inflammatory actions in various inflammatory diseases. Maresin-1 is a derivative of one of the representative omega-3 fatty acids, i.e., docosahexaenoic acid (DHA), and has shown beneficial action in inflammatory disease models. In this review, we summarize the detailed actions of maresin-1 in immune cells and inflammatory diseases.

[A Case of a Subcutaneous Foreign Body Discovered by Coincidence During a Head MRI Imaging Examination].

An 80-year-old male was admitted to the department of neurology for intensive examination and treatment of peri-optic nerve inflammation. Magnetic resonance imaging examination could not be conducted because a magnetic resonance imaging examination at a previous clinic revealed a subcutaneous foreign body on his head, possibly a piece of metal. He was referred to our department for the removal of this foreign body. There was no traumatic scar in the skin and we could not identify this subcutaneous foreign body by physical examination and superficial echography, but radioscopy could find this subcutaneous material and we could remove this foreign body under the guidance of the radioscopy.

Daily Lifestyle and Inflammatory Skin Diseases.

Throughout life, it is necessary to adapt to the Earth's environment in order to survive. A typical example of this is that the daily Earth cycle is different from the circadian rhythm in human beings; however, the ability to adapt to the Earth cycle has contributed to the development of human evolution. In addition, humans can consume and digest Earth-derived foods and use luxury materials for nutrition and enrichment of their lives, as an adaptation to the Earth's environment. Recent studies have shown that daily lifestyles are closely related to human health; however, less attention has been paid to the fact that obesity due to excessive energy intake, smoking, and alcohol consumption contributes to the development of inflammatory skin diseases. Gluten or wheat protein, smoking and alcohol, sleep disturbance, and obesity drive the helper T (Th)1/Th2/Th17 immune response, whereas dietary fiber and omega-3 fatty acids negatively regulate inflammatory cytokine production. In this review, we have focused on daily lifestyles and the mechanisms involved in the pathogenesis of inflammatory skin diseases.

The Role of IL-17-Producing Cells in Cutaneous Fungal Infections.

The skin is the outermost layer of the body and is exposed to many environmental stimuli, which cause various inflammatory immune responses in the skin. Among them, fungi are common microorganisms that colonize the skin and cause cutaneous fungal diseases such as candidiasis and dermatophytosis. The skin exerts inflammatory responses to eliminate these fungi through the cooperation of skin-component immune cells. IL-17 producing cells are representative immune cells that play a vital role in anti-fungal action in the skin by producing antimicrobial peptides and facilitating neutrophil infiltration. However, the actual impact of IL-17-producing cells in cutaneous fungal infections remains unclear. In this review, we focused on the role of IL-17-producing cells in a series of cutaneous fungal infections, the characteristics of skin infectious fungi, and the recognition of cell components that drive cutaneous immune cells.

The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies.

Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and has been identified as a tumor suppressor gene. CADM1 has multifunctions on the pathogenesis of malignancies, and other normal cells such as immune cells. However, little is known about the function of CADM1 on cutaneous cells and cutaneous malignancies. CADM1 plays an important role in connecting cells with each other, contacting cells to deliver their signal, and acting as a scaffolding molecule for other immune cells to develop their immune responses. A limited number of studies reveal the contribution of CADM1 on the development of cutaneous malignancies. Solid cutaneous malignancies, such as cutaneous squamous cell carcinoma and malignant melanoma, reduce their CADM1 expression to promote the invasion and metastasis of the tumor. On the contrary to these cutaneous solid tumors except for Merkel cell carcinoma, cutaneous lymphomas, such as adult-T cell leukemia/lymphoma, mycosis fungoides, and Sézary syndrome, increase their CADM1 expression for the development of tumor environment. Based on the role of CADM1 in the etiology of tumor development, the theory of CADM1 contribution will desirably be applied to skin tumors according to other organ malignancies, however, the characteristics of skin as a multicomponent peripheral organ should be kept in mind to conclude their prognoses.

Drug eruption caused by enzalutamide: A case and literature review of androgen receptor inhibitor-related drug eruptions.

Enzalutamide is an androgen receptor inhibitor. We report a new cutaneous eruption to this drug and review cases of drug eruptions caused by androgen receptor inhibitors.

First case of drug eruption due to ipragliflozin: Case report and review of the literature.

Ipragliflozin is a new drug for the treatment of diabetes mellitus. Its action of sodium-glucose cotransporter 2 (SGLT2) inhibition induces glucosuria and decreases blood glucose levels. We report the first case of ipragliflozin-related eczematous drug eruption and a review of the past literature on drug eruptions caused by SGLT2 inhibitors.

Purpuric Type Drug Eruption Caused by Azithromycin: A Case Report and Literature Review.

Azithromycin, an azolide antibiotic with structural and functional similarities to macrolides, possesses distinct features such as its effects persisting for seven days, an extended half-life by administering it once daily for three days, and strong antimicrobial activity. Notably, vomiting and diarrhea are recognized as the primary adverse events related to azithromycin. In this particular case, we present a unique case describing a purpuric-type drug eruption associated with azithromycin, which represents an uncommon cutaneous manifestation. A 64-year-old female developed a purpuric eruption on her trunk and lower extremities seven days after receiving daily intravenous azithromycin for upper bronchitis. A previous occurrence of punctate purpuric eruption following azithromycin administration was documented in her medical history. The diagnosis of azithromycin-induced skin eruption was confirmed based on the clinical progression and the recurrence of the eruption upon re-administration of the drug. In response to this diagnosis, the patient underwent treatment involving the discontinuation of azithromycin and the application of topical betamethasone butyrate propionate ointment. Remarkably, her eruption significantly improved within two weeks, although residual pigmentation persisted post-treatment. Additionally, we offer a comprehensive review of the literature, examining cases of drug eruptions related to azithromycin.

Recurrent Merkel Cell Carcinoma Following COVID-19 Treatment.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer influenced by the immune system. Recent studies suggest that viral infections, notably COVID-19, may exacerbate such malignancies. This case report explores potential mechanisms by which SARS-CoV-2, the virus responsible for COVID-19, could influence the behavior and proliferation of malignant tumor cells. Emerging evidence indicates that COVID-19 may disrupt immune surveillance and modulation, which are critical in controlling the spread and severity of cancers, including MCC. Additionally, the cytokine storm induced by COVID-19 is proposed to facilitate tumorigenic activity, potentially enhancing MCC aggressiveness. By integrating clinical findings with contemporary immunological and virological theories, this report aims to contribute to the understanding of COVID-19's impact on cancer progression, specifically MCC, emphasizing the need for comprehensive management strategies in cancer patients during the pandemic.

Toxic Epidermal Necrolysis Caused by Eribulin.

Eribulin, a chemotherapy drug classified as a microtubule inhibitor, is known to target cell microtubule structures, impeding cancer cell growth and spread. This paper discusses a rare case of toxic epidermal necrolysis (TEN) induced by eribulin in a patient with angiosarcoma, marking it as an uncommon adverse reaction. This patient developed severe mucosal and skin lesions after the third dose of eribulin. Laboratory tests and a skin biopsy confirmed the diagnosis of TEN. The patient responded well to steroid therapy, although skin eruptions reoccurred with further eribulin treatment. This case highlights the need for further study on the immunological effects of eribulin, especially concerning severe drug eruptions potentially related to its impact on microtubule dynamics and immune cell functions.

Spesolimab in the Management of Generalized Pustular Psoriasis With Concurrent Bullous Pemphigoid and Psoriasis.

Autoimmune diseases often co-occur due to shared immunological mechanisms, necessitating strategic treatment approaches to manage overlapping conditions without exacerbating each other. A 75-year-old male with a history of psoriasis vulgaris and bullous pemphigoid (BP) developed new-onset pustular psoriasis under systemic corticosteroid therapy, which is known to potentially worsen psoriasis into its pustular form. Histological examination confirmed the diagnosis, showing features typical of pustular psoriasis. The patient was successfully treated with spesolimab, an anti-IL-36 neutralizing antibody, achieving complete remission without aggravating the BP. This case highlights the necessity of cautious treatment selection in patients with multiple autoimmune disorders and underscores the potential role of IL-36 in exacerbating inflammatory responses in BP. Further research into the interaction between IL-36 and BP may provide deeper insights into managing such complex clinical scenarios.

A Case Report of Mycosis Fungoides Presenting With Blister Formation.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma with a usually indolent course. Early detection is crucial for effective intervention. We present a case of a 40-year-old male with MF exhibiting blistering as a rare precursor symptom. Despite initial treatment for eczema, the condition worsened over 10 months, leading to erythema, edema, and enlarged lymph nodes. Laboratory and imaging findings confirmed the diagnosis of MF. The patient responded partially to cyclophosphamide/doxorubicin/prednisone in combination with brentuximab vedotin (A-CHP) therapy. This case highlights the significance of recognizing blistering as a prodromal symptom for early detection and management of MF.

Malignant Melanoma With Neural Marker-Positive Distant Organ Cancers.

Malignant melanoma is a melanocyte-derived tumor known for its aggressive clinical behavior. Melanocytes originate from the neural crest, which also gives rise to neural tissues. Malignant melanoma can occasionally exhibit neural differentiation. We report a case of a 70-year-old male with malignant melanoma exhibiting neural marker positivity in the absence of typical melanoma markers. The patient initially presented with a dark nodule on his left heel, which was confirmed as malignant melanoma through cytology. Surgical resection and lymph node dissection were performed, revealing atypical melanocytes. Despite postoperative nivolumab treatment, metastases in the brain and lungs were observed. Histological examination of the brain tumor showed neural differentiation markers (thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK7), AE1/AE3, and epidermal growth factor receptor (EGFR)) with negative melanoma markers. The patient eventually succumbed to the disease despite multiple treatments. An autopsy revealed multiple organ tumors (brain, duodenum, stomach, liver, and bile duct) negative for melanoma markers but positive for neuroendocrine markers (CD56, synaptophysin, and chromogranin A). This case suggests two possibilities: the coexistence of malignant melanoma with neuroendocrine tumors or a transformation of melanoma into a neuroendocrine phenotype. This case highlights the need for clinicians to consider the potential for melanoma to lose typical markers and transform into neuroendocrine cancer.

The Development of Systemic Inflammatory Diseases in Hidradenitis Suppurativa.

It is understood that the skin is a peripheral lymphoid tissue that defends against external environmental stimuli. Continuous activation from these factors, on the other hand, promotes persistent inflammation at the local location and, occasionally, tissue damage. Hidradenitis suppurativa (HS) is a typical inflammatory skin disease and becomes a source of numerous inflammatory cytokines due to the chronic intractable repeated inflamed tissues. Because inflammatory cells and cytokines circulate throughout the body from the inflamed organ, it has been hypothesized that HS-mediated skin inflammation impacts the systemic functioning of numerous organs. Recent updates to clinical and experimental investigations revealed that HS has a significant connection with systemic inflammatory disorders. We provide the details and comprehensive molecular mechanisms associated with systemic inflammatory illnesses due to HS.

S100 Proteins in the Pathogenesis of Psoriasis and Atopic Dermatitis.

The skin, the outermost layer of the human body, is exposed to various external stimuli that cause inflammatory skin reactions. These external stimulants trigger external epithelial cell damage and the release of intracellular substances. Following cellular damage or death, intracellular molecules are released that enhance tissue inflammation. As an important substance released from damaged cells, the S100 protein is a low-molecular-weight acidic protein with two calcium-binding sites and EF-hand motif domains. S100 proteins are widely present in systemic organs and interact with other proteins. Recent studies revealed the involvement of S100 in cutaneous inflammatory disorders, psoriasis, and atopic dermatitis. This review provides detailed information on the interactions among various S100 proteins in inflammatory diseases.

Co-occurrence of Malignant Melanoma and Squamous Cell Carcinoma on Burn Scars: A Case Report.

Tumors arising from burn scars are not rare but sometimes cause the rare co-existence of different tumors. However, detailed information on this topic remains largely unknown. We present a case of the co-occurrence of malignant melanoma and squamous cell carcinoma in a patient with a history of burn scars. A 73-year-old man presented with an erythematous plaque on his left lower leg that gradually turned into a tumor with ulceration. He also presented with scaly tumors at other sites within the same burn scar lesion. He had a history of burns on the left leg at the age of 20 years. After surgical resection of the tumors, histological analysis revealed that the posterior aspect of the largest tumor was malignant melanoma, and the remaining two tumors were squamous cell carcinomas, indicating the co-existence of different types of malignant skin cancers. Based on a literature review of previously published case reports, this is the first report to highlight the importance of complete skin grafts in reducing this risk.

Ixekizumab-induced urticarial drug eruption.

Biological agents targeting inflammatory skin diseases have dramatically overcome many of the limitations of older oral therapeutic options. Among the various biological agents, ixekizumab is a humanised monoclonal antibody that blocks the biological activity of IL-17A, which exhibited high efficacy against psoriasis. Although there are a limited number of cutaneous adverse reactions, biologic-induced type I allergic reactions are rare. Herein, we report a case of ixekizumab-induced urticaria.