Eosinophilic Dermatosis of Hematologic Malignancy: Emerging Evidence for the Role of Insect Bites-A Retrospective Clinico-Pathological Study of 35 Cases.

Background/Objectives: Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous disorder associated with various hematologic malignancies, most commonly chronic lymphocytic leukemia. Detailed clinicopathologic studies of EDHM are lacking and the pathogenesis remains enigmatic. Initially thought to be a hypersensitivity reaction to insect stings, subsequent reports have challenged this understanding. The prognostic implications of EDHM remain unclear. Methods: A retrospective clinicopathologic study was performed on patients diagnosed with EDHM. Hematologic and dermatologic data were reviewed. Histologic specimens were re-evaluated and lesions were classified into acute/subacute, fully developed, and chronic/regressing. Results: The study included 35 patients. In 80% of these patients, EDHM was diagnosed after the hematologic disorder. Approximately 45% of the cohort experienced hematologic disease progression or relapse, while 65% required therapeutic intervention during the course of their hematologic disease. In total, 15/19 CLL patients had non-mutated IgHV, a marker of a more aggressive hematologic disease course. Dermatologic lesion morphology was heterogeneous, with most lesions occurring on exposed areas, and a significant 94% of patients demonstrated lesion seasonality. Histopathologic findings were consistent with features typically associated with insect bites. In addition, examination of lesions at different chronological stages revealed substantial similarities with Wells syndrome. Conclusions: Our findings support the potential role of insect bites in triggering EDHM in the context of adaptive immune dysfunction. EDHM may be associated with a more aggressive disease course or may be a marker of disease progression. The observed co-occurrence of features typical of Wells syndrome in EDHM patients suggests that these conditions are part of a spectrum of disorders that vary in clinical expression.

Galli-Galli Disease: A Comprehensive Literature Review.

Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD's first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the KRT5 and POGLUT1 genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments.

Eosinophilic dermatosis of hematologic malignancy in patients with chronic lymphocytic leukemia/non-Hodgkin's B lymphoma: a single center prospective clinico-pathological study.

Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be responsible. Its prognostic significance is unclear. Objective: To describe the clinical, pathological and immunological findings in a series of oncohematological patients with EDHM. Methods: An observational prospective cohort study of oncohematological patients receiving a diagnosis of EDHM between April 2017 and December 2018. Results: A total of 15 patients with EDHM (10 females and 5 males) were identified among 422 oncohematological patients. Disease presentation varied from firm erythematous papules to more polymorphic presentations. The lesions were most prevalent on the exposed sites, 8/15 patients recalled an insect bite. Lesion seasonality was reported in 13/15 patients. IgE levels were elevated in six patients, circulating IL-4 and IL-5 were within a normal range. Twelve out of 15 patients developed skin manifestations after chemotherapy. The infiltrate could be eosinophil-rich or lymphocytic-rich. Interestingly, the histopathologic findings were in accordance with arthropod bites. Conclusion: A role for insect bites in EDHM is supported by our findings. EDHM may be related to aggressive hematologic disease.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

Clinical Challenges in Primary Erythromelalgia: a Real-Life Experience from a Single Center and a Diagnostic-Therapeutic Flow-Chart Proposal.

INTRODUCTION: Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise the patients' quality of life leading to severe disability. SCN9A mutations can be the cause of the disease. Dermatologists are often the specialists these patients turn to for assistance. OBJECTIVES: To describe the demographic and clinical characteristics of patients with primary EM, to assess the presence and mutation types in the SCN9A gene, to evaluate the effectiveness of several therapeutic approaches, and to propose a diagnostic algorithm with therapeutic implications. METHODS: A monocentric retrospective study using the database of patients with a discharge diagnosis of primary EM of our Center. Demographic, clinical, instrumental and laboratory data of patients were reviewed. RESULTS: Eleven female patients (age range 16 to 57) were selected. All patients were affected in both the lower and upper extremities. Follow-up ranged from 2 to 9 years. Four patients had four different heterozygous variants of the SCN9A gene. Two patients, although genetically negative, had a suggestive family history. A variety of medications were tried in all our patients to alleviate symptoms, but their efficacy was variable, partial and/or transitory. The most effective therapies were antihistamines, venlafaxine, and mexiletine. CONCLUSIONS: The diagnosis and treatment of EM remain challenging. Patients with this condition display a wide spectrum of clinical manifestations and severity, as well as a paucity of resources and structures to support them. Mutations in the SCN9A gene are not always detected.

A Clinico-Pathological Multidisciplinary Team Increases the Efficacy of Skin Biopsy and Reduces Clinical Risk in Dermatology.

A clinical risk is an inherent risk in healthcare processes, including skin biopsy procedures, and may lead to misdiagnoses, increased healthcare costs and potential harm to patients. Indeed, clinical and histopathological data must be integrated if we are to reduce clinical risks and improve diagnostic accuracy in the diagnosis of dermatologic diseases. Although dermopathology services used to be part of a dermatologist's duty, the recent centralization of these laboratories has caused a loss of expertise and increased both complexity and safety issues. Some countries have implemented clinical-pathological correlation programs aimed at facilitating communication between clinicians and dermatopathologists. However, Italy has regulatory and cultural barriers that make the implementation of these programs difficult. Therefore, an internal analysis was carried out to assess the efficacy and impact that skin biopsy procedures for inflammatory and neoplastic conditions have on the quality of care in our dermatology department. As the analysis evidenced a high number of descriptive pathologic reports and discordant diagnoses, a multidisciplinary group of four dermatologists, four general pathologists and one dermatopathologist was set up. Herein, we present the results of this analysis and project and describe the structure of the multidisciplinary group. We also discuss the pros and cons, possibilities and limitations of our project, including the regulatory barriers of the Italian National Health System.

Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series.

An "atypical exanthem" (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.

Blisters and Milia around the Peritoneal Dialysis Catheter: A Case of Localized Bullous Pemphigoid.

We report on the appearance of multiple tense blisters surrounding the exit site of a Tenckhoff catheter in a 79-year-old woman with end-stage renal disease in peritoneal dialysis. The differential diagnoses included a contact allergic or irritative dermatitis to peritoneal dialysis catheter material and antiseptic agents, bacterial infection, and herpes virus infection, but milia were a clue for a subepidermal blistering disease and lead to appropriate investigations. The laboratory findings, the histopathological examination and the direct immunofluorescence assay confirmed the diagnosis of localized bullous pemphigoid. The disorder typically occurs in elderly people and may be related to drugs, hematological malignancies or neurological conditions but it can also be a complication of hemodialysis or peritoneal dialysis.

An Ecchymosis with Fulminant Evolution.

We present the case of an 83-year-old woman who presented with an advanced cutaneous angiosarcoma of the head. The tumor had first appeared as a small ecchymosis on her forehead 3 months before admission. There was an extremely rapid and dramatic evolution, as evidenced by photographic documentation by her relatives. Unfortunately, the delay in access to the healthcare system due to the COVID-19 pandemic lockdown and the fulminant growth were the main determinants for our patient outcome.

Erosive Pustular Dermatosis of the Scalp: A Clinicopathologic Study of Fifty Cases.

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon, pustular, idiopathic disorder typically occurring on the scalp of the elderly, whose diagnosis requires close clinicopathologic correlations. Recently, the primary histopathologic characteristic of EPDS has been identified in some biopsies from hair-bearing scalp lesions as a sterile, vesiculo-pustule involving the infundibulum of hair follicles. To further delineate the clinicopathologic spectrum of the disease, we led a retrospective study of 50 patients (36 males and 14 females) with a diagnosis of EPDS between 2011 and 2021, reviewing clinical and histopathological data. Androgenetic alopecia was present in 32 patients. Triggering factors were present in 21 patients. The vertex was the most common location; one patient also had leg involvement. Two cases were familial. Disease presentation varied markedly from tiny, erosive, scaly lesions to crusted and hemorrhagic plaques, mimicking pustular pyoderma gangrenosum (PPG). Biopsies of patients with severe androgenetic or total baldness produced specimens showing nonspecific pathologic changes (39/50), while in 11 patients with a hair-bearing scalp histopathologic examination, changes were specific. The clinicopathologic similarities between EPDS and PPG suggest that EPDS should be included in the spectrum of autoinflammatory dermatoses. Clinicians could consider the possibility of associated disorders rather than managing EPDS as a sui generis skin disorder.

Spiky/keratosis-pilaris-like early follicular mycosis fungoides: A clinicopathologic study of 20 cases with extended follow-up.

BACKGROUNDS: Follicular mycosis fungoides (FMFs) is a distinct form of T-cell lymphoma whose course is considered aggressive. METHODS: A retrospective study with long-term follow-up of 20 patients diagnosed with spiky/keratosis-pilaris-like FMF between 2008 and 2017 was conducted. RESULTS: Twelve males and eight females were identified, with a mean age at first diagnosis of 59 years (range 42-86). Hyperkeratotic follicular papules were the sole clinical finding in 16 of 20 patients. A diagnostic delay between first symptom development and initial diagnosis was frequent (mean 42 months). The head/neck region was concurrently affected only in two patients. Disease stage at diagnosis was IA in two patients (10%) and IB in 18 (90%). Five patients had almost complete lesion regression, whilst there was only a slight improvement, without regression in 14. Two patients developed infiltrated papules, comedones, and small cysts during follow-up. Only one patient progressed to tumor stage (IIB) five years after the first diagnosis. The mean follow-up was seven years (range: 12-180 months). None of them died of cutaneous lymphoma. CONCLUSIONS: FMF presenting with only spiky/keratosis-pilaris-like lesions have an excellent prognosis at medium-term follow-up. Early recognition of patients with this peculiar FMF presentation might lead to identifying prognostic factors.