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Chaudhary F, Lee W, Escander T, Agrawal DK. Exploring the Complexities of Atopic Dermatitis: Pathophysiological Mechanisms and Therapeutic Approaches. JOURNAL OF BIOTECHNOLOGY AND BIOMEDICINE 2024; 7:314-328. [PMID: 39119011 PMCID: PMC11309089 DOI: 10.26502/jbb.2642-91280155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
Atopic dermatitis (AD) is a prevalent inflammatory skin condition impacting both children and adults globally, with a prevalence of 15-30%. It ranks as the most prevalent skin disorder based on disability-adjusted life-years by the World Health Organization. It presents with symptoms like skin irritation, redness, dryness, itchiness, and vesicular blisters and commonly coexists with other atopic symptoms like allergic rhinitis, asthma, and food allergies. The pathophysiology involves a complex interplay of genetic predispositions, immunological dysfunctions, and environmental factors leading to tissue inflammation and disrupted skin barrier integrity. Alopecia areata is characterized by nonscarring hair loss and shares correlations with AD including a higher prevalence of atopic diseases, shared intracellular mechanisms involving the JAK-STAT pathway, and potential treatment overlap such as dupilumab. These correlations could direct new areas of research and increased insight for both diseases. Treatment of AD requires a personalized approach due to its complex, multifactorial nature integrating nonpharmacological interventions like skin hydration and trigger avoidance as well as topical and systemic approaches, if necessary, with topical corticosteroids being the first line for flares; long term corticosteroid use poses risk for adverse effects like skin atrophy. Severe cases may require systemic treatments or phototherapy. Future treatment prospects include targeting the dysbiotic microbiome and identifying biomarkers for tailored therapeutic strategies, emphasizing the importance of personalized medicine in optimizing AD management.
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Affiliation(s)
- Fihr Chaudhary
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona CA 91766, USA
| | - Wismmy Lee
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona CA 91766, USA
| | - Tony Escander
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona CA 91766, USA
| | - Devendra K Agrawal
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona CA 91766, USA
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Riedl R, Kühn A, Hupfer Y, Hebecker B, Peltner LK, Jordan PM, Werz O, Lorkowski S, Wiegand C, Wallert M. Characterization of Different Inflammatory Skin Conditions in a Mouse Model of DNCB-Induced Atopic Dermatitis. Inflammation 2024; 47:771-788. [PMID: 38150167 DOI: 10.1007/s10753-023-01943-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 11/10/2023] [Accepted: 12/04/2023] [Indexed: 12/28/2023]
Abstract
The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds. However, the study designs and methods are highly diverse, presenting different hlAD disease patterns that occur after sensitization and repeated challenge with DNCB on dorsal skin. In addition, there is a lack of information about the progression of the disease during the experiment and the achieved pheno- and endotypes, especially at the timepoint when therapeutic treatment is initiated. We here examine hlAD in a DNCB-induced BALB/cJRj model at different timepoints: (i) before starting treatment with dexamethasone, representing a standard drug control (day 12) and (ii) at the end of the experiment (day 22). Both timepoints display typical AD-associated characteristics: skin thickening, spongiosis, hyper- and parakeratosis, altered cytokine and gene expression, increased lipid mediator formation, barrier protein and antimicrobial peptide abnormalities, as well as lymphoid organ hypertrophy. Increased mast cell infiltration into the skin and elevated immunoglobulin E plasma concentrations indicate a type I allergy response. The DNCB-treated skin showed an extrinsic moderate sub-acute hlAD lesion at day 12 and an extrinsic mild sub-acute to chronic pheno- and endotype at day 22 with a dominating Th2 response. A dependency of the filaggrin formation and expression in correlation to the disease severity in the DNCB-treated skin was found. In conclusion, our study reveals a detailed classification of a hlAD at two timepoints with different inflammatory skin conditions and pheno- and endotypes, thereby providing a better understanding of the DNCB-induced hlAD model in BALB/cJRj mice.
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Affiliation(s)
- Rebecca Riedl
- Department of Dermatology, Dermatological Research Laboratory, Jena University Hospital, 07747, Jena, Germany
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany
| | - Annika Kühn
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany
| | - Yvonne Hupfer
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany
| | - Betty Hebecker
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, 07743, Jena, Germany
| | - Lukas K Peltner
- Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, 07743, Jena, Germany
| | - Paul M Jordan
- Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, 07743, Jena, Germany
- Jena Center for Soft Matter (JCSM), Friedrich Schiller University, 07743, Jena, Germany
| | - Oliver Werz
- Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, 07743, Jena, Germany
- Jena Center for Soft Matter (JCSM), Friedrich Schiller University, 07743, Jena, Germany
| | - Stefan Lorkowski
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, 07743, Jena, Germany
| | - Cornelia Wiegand
- Department of Dermatology, Dermatological Research Laboratory, Jena University Hospital, 07747, Jena, Germany
| | - Maria Wallert
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Science, Friedrich Schiller University, 07743, Jena, Germany.
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, 07743, Jena, Germany.
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Han J, Owji S, Agarwal A, Kamat S, Luu Y, Mubasher A, Niedt G, Ray C, Cho HJ, Gulati N, Lamb A. Bortezomib-Induced Reticular Eruption in Patient with Multiple Myeloma. Dermatopathology (Basel) 2023; 10:226-230. [PMID: 37489455 PMCID: PMC10366922 DOI: 10.3390/dermatopathology10030031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 07/06/2023] [Accepted: 07/17/2023] [Indexed: 07/26/2023] Open
Abstract
Bortezomib is the first proteasome inhibitor to treat a variety of malignancies and is currently part of the standard of care regimen for the initial treatment of patients with newly diagnosed multiple myeloma. While bortezomib is generally well tolerated, it has been associated with various side effects, which have limited its use in some patients. Here, we describe a unique case with histological confirmation of a reticular eruption that appeared at the site of a subcutaneous administration of bortezomib in a 62-year-old male who was newly diagnosed with IgG kappa multiple myeloma. A skin biopsy was performed, which revealed superficial perivascular dermatitis predominantly composed of lymphocytes with rare eosinophils. The patient was successfully treated with betamethasone dipropionate 0.05% cream. When consulted, dermatologists should advise the oncology team of multiple myeloma patients treated with bortezomib to maintain a high threshold before discontinuing the drug when a patient experiences an atypical, reticular rash following subcutaneous administration. Additionally, potent topical corticosteroids, such as betamethasone dipropionate 0.05% cream, should be considered in managing the cutaneous reticular eruptions related to bortezomib administration, in order to maintain an optimal treatment regimen for patients with multiple myeloma.
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Affiliation(s)
- Joseph Han
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Shayan Owji
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Aneesh Agarwal
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Samir Kamat
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yen Luu
- School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Adnan Mubasher
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - George Niedt
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Chloe Ray
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Hearn Jay Cho
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Nicholas Gulati
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Angela Lamb
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Sirbu CA, Ivan R, Vasile TM, Eftimie LG, Costache DO. Cutaneous Adverse Reactions Associated with Monoclonal Antibodies Treatment in Multiple Sclerosis: Case Reports and Short Literature Review. J Clin Med 2022; 11:jcm11133702. [PMID: 35806991 PMCID: PMC9267819 DOI: 10.3390/jcm11133702] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/17/2022] [Accepted: 06/25/2022] [Indexed: 02/05/2023] Open
Abstract
Background and aims. Multiple sclerosis is a disease of the central nervous system, whose treatment often involves the use of monoclonal antibodies. This can lead to a series of complications that the clinician should pay attention to and accordingly adjust the therapy. We aim to emphasize real-life experiences with adverse cutaneous reactions to monoclonal antibodies by presenting a series of two cases from our clinic. Methods. In the first case, a female patient was treated with natalizumab for eight years and developed relapsing-remitting cutaneous lesions following the monthly administration of the treatment. The second case is of a male patient treated with ocrelizumab, who developed plaque-like lesions following the fifth administration. We analyzed the biological parameters and performed investigations, dermatological evaluation and skin biopsies. Results. The result of the skin biopsy for the natalizumab patient showed a chronic spongiotic dermatitis, with the anti-natalizumab antibodies being negative. The patient who received ocrelizumab developed nummular eczema, disseminated on his trunk and limbs. Conclusions. Given the fact that these therapies are frequently used in multiple sclerosis patients, and their skin adverse reactions are known, we described some particularities and a brief review of the literature with practical implications. Further studies need to be conducted to establish a firm association between monoclonal antibodies therapy and adverse cutaneous reactions, but the clinician should be aware of their existence.
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Affiliation(s)
- Carmen Adella Sirbu
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania; (C.A.S.); (R.I.)
| | - Raluca Ivan
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania; (C.A.S.); (R.I.)
| | - Titus Mihai Vasile
- Clinical Neurosciences Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania
- Correspondence: (T.M.V.); (L.G.E.)
| | - Lucian George Eftimie
- Department of Pathology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Correspondence: (T.M.V.); (L.G.E.)
| | - Daniel Octavian Costache
- Department of Dermatology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania;
- 2nd Dermatology Discipline, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania
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Balan R, Grigoraş A, Popovici D, Amălinei C. The histopathological landscape of the major psoriasiform dermatoses. Arch Clin Cases 2021; 6:59-68. [PMID: 34754910 PMCID: PMC8565680 DOI: 10.22551/2019.24.0603.10155] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category, followed by pustular psoriasis, Reiter's syndrome, pityriasis rubra pilaris, lichen simplex chronicus and large-plaques parapsoriasis. They create a diagnostic challenge, both clinical and histopathological, because of their complexity and frequent overlapping of the microscopical features. The characteristic histopathological features of psoriasiform reaction comprise extensive hyperkeratosis, with horizontally confluent but vertically intermittent parakeratosis, which alternate with orthokeratosis, thin granular layer, with relative frequent mitoses, uniform elongated and fused rete ridges, edematous superficial papillary dermis, with dilated capillaries, perivascular lymphocytic infiltrate, Munro's microabscesses, and spongiform pustules of Kogoj. Our paper aims to review the histopathology of major form of psoriasiform dermatoses and to emphasize the characteristic microscopical differences between them, for a better approach of the diagnosis as an important key for clinical and therapeutical management. Using the clinicopathological correlations, a thoroughly evaluation of the microscopical features and compartments distribution or special stainings and techniques, the range of differential diagnosis can be decreased and a more accurate diagnostic can be usually achieved. The insights into the pathogenic mechanisms can lead to new therapeutic opportunities targeted to the specific type of inflammatory lesion.
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Affiliation(s)
- Raluca Balan
- Department of Morphofunctional Sciences I - Histology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Adriana Grigoraş
- Department of Morphofunctional Sciences I - Histology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Diana Popovici
- Department - Medicine of Mother and Child, "Grigore T. Popa" University of Medicine and Pharmacy, Iaşi, Romania
| | - Cornelia Amălinei
- Department of Morphofunctional Sciences I - Histology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
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Braegelmann C, Niebel D, Ferring-Schmitt S, Fetter T, Landsberg J, Hölzel M, Effern M, Glodde N, Steinbuch S, Bieber T, Wenzel J. Epigallocatechin-3-gallate exhibits anti-inflammatory effects in a human interface dermatitis model-implications for therapy. J Eur Acad Dermatol Venereol 2021; 36:144-153. [PMID: 34585800 DOI: 10.1111/jdv.17710] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/15/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Epigallocatechin-3-gallate (EGCG) has been proven effective in treating viral warts. Since anticarcinogenic as well as anti-inflammatory properties are ascribed to the substance, its use has been evaluated in the context of different dermatoses. The effect of EGCG on interface dermatitis (ID), however, has not yet been explored. OBJECTIVES In this study, we investigated the effect of EGCG on an epidermal human in vitro model of ID. METHODS Via immunohistochemistry, lesional skin of lichen planus patients and healthy skin were analysed concerning the intensity of interferon-associated mediators, CXCL10 and MxA. Epidermal equivalents were stained analogously upon ID-like stimulation and EGCG treatment. Monolayer keratinocytes were treated likewise and supernatants were analysed via ELISA while cells were processed for vitality assay or transcriptomic analysis. RESULTS CXCL10 and MxA are strongly expressed in lichen planus lesions and induced in keratinocytes upon ID-like stimulation. EGCG reduces CXCL10 and MxA staining intensity in epidermis equivalents and CXCL10 secretion by keratinocytes upon stimulation. It furthermore minimizes the cytotoxic effect of the stimulus and downregulates a magnitude of typical pro-inflammatory cytokines that are crucial for the perpetuation of ID. CONCLUSIONS We provide evidence concerning anti-inflammatory effects of EGCG within a human in vitro model of ID. The capacity to suppress mediators that are centrally involved in disease perpetuation suggests EGCG as a potential topical therapeutic in lichen planus and other autoimmune skin diseases associated with ID.
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Affiliation(s)
- C Braegelmann
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - D Niebel
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - S Ferring-Schmitt
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - T Fetter
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - J Landsberg
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - M Hölzel
- Institute of Experimental Oncology (IEO), University Hospital Bonn, Bonn, Germany
| | - M Effern
- Institute of Experimental Oncology (IEO), University Hospital Bonn, Bonn, Germany
| | - N Glodde
- Institute of Experimental Oncology (IEO), University Hospital Bonn, Bonn, Germany
| | - S Steinbuch
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - T Bieber
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
| | - J Wenzel
- Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany
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Ossama M, Lamie C, Tarek M, Wagdy HA, Attia DA, Elmazar MM. Management of recurrent aphthous ulcers exploiting polymer-based Muco-adhesive sponges : in-vitro and in-vivo evaluation. Drug Deliv 2021; 28:87-99. [PMID: 33342321 PMCID: PMC7758044 DOI: 10.1080/10717544.2020.1858999] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.
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Affiliation(s)
- Muhammed Ossama
- Department of Pharmaceutics and Pharmaceutical Technology, The British University in Egypt (BUE), Cairo, Egypt
| | - Caroline Lamie
- Department of Pharmaceutics and Pharmaceutical Technology, The British University in Egypt (BUE), Cairo, Egypt
| | - Mohamed Tarek
- Department of Pharmaceutical Chemistry, The British University in Egypt (BUE), Cairo, Egypt
| | - Hebatallah A Wagdy
- Department of Pharmaceutical Chemistry, The British University in Egypt (BUE), Cairo, Egypt
| | - Dalia A Attia
- Department of Pharmaceutics and Pharmaceutical Technology, The British University in Egypt (BUE), Cairo, Egypt
| | - Mohamed M Elmazar
- Department of Pharmacology and Biochemistry, The British University in Egypt (BUE), Cairo, Egypt
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Zimmermann N, Abonia JP, Dreskin SC, Akin C, Bolton S, Happel CS, Geller M, Larenas-Linnemann D, Nanda A, Peterson K, Wasan A, Wechsler J, Zhang S, Bernstein JA. Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee. J Allergy Clin Immunol 2021; 148:964-983. [PMID: 34384610 DOI: 10.1016/j.jaci.2021.06.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 10/20/2022]
Abstract
Mast cells and eosinophils are commonly found, expectedly or unexpectedly, in human tissue biopsies. Although the clinical significance of their presence, absence, quantity, and quality continues to be investigated in homeostasis and disease, there are currently gaps in knowledge related to what constitutes quantitatively relevant increases in mast cell and eosinophil number in tissue specimens for several clinical conditions. Diagnostically relevant thresholds of mast cell and eosinophil numbers have been proposed and generally accepted by the medical community for a few conditions, such as systemic mastocytosis and eosinophilic esophagitis. However, for other mast cell- and eosinophil-associated disorders, broad discrepancies remain regarding diagnostic thresholds and how samples are processed, routinely and/or specially stained, and interpreted and/or reported by pathologists. These discrepancies can obfuscate or delay a patient's correct diagnosis. Therefore, a work group was assembled to review the literature and develop a standardized consensus for assessing the presence of mast cells and eosinophils for a spectrum of clinical conditions, including systemic mastocytosis and cutaneous mastocytosis, mast cell activation syndrome, eosinophilic esophagitis, eosinophilic gastritis/enteritis, and hypereosinophilia/hypereosinophilic syndrome. The intent of this work group is to build a consensus among pathology, allergy, dermatology, hematology/oncology, and gastroenterology stakeholders for qualitatively and quantitatively assessing mast cells and eosinophils in skin, gastrointestinal, and bone marrow pathologic specimens for the benefit of clinical practice and patients.
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Affiliation(s)
- Nives Zimmermann
- Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - J Pablo Abonia
- Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
| | - Stephen C Dreskin
- Division of Allergy and Immunology, Department of Internal Medicine, University of Colorado, Aurora, Colo
| | - Cem Akin
- Division of Allergy and Immunology, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich
| | - Scott Bolton
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Corinne S Happel
- Division of Allergy and Immunology, Department of Internal Medicine, John Hopkins School of Medicine, Baltimore, Md
| | - Mario Geller
- Department of Medicine, the Academy of Medicine of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Anil Nanda
- Asthma and Allergy Center, Lewisville, Tex; Asthma and Allergy Center, Flower Mound, Tex; Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex
| | - Kathryn Peterson
- Division of Gastroenterology, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah
| | - Anita Wasan
- Division of Gastroenterology, Hepatology, and Nutrition, Allergy and Asthma Center, McLean, Va
| | - Joshua Wechsler
- Division of Allergy and Immunology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
| | - Simin Zhang
- Allergy Section, Division of Immunology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Jonathan A Bernstein
- Allergy Section, Division of Immunology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
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Wegner J, Weidenthaler-Barth B, Engelbert J, Knothe M, Braun C, Helbig D, Sacher C, Kreft A, Wagner EM, Ziemer M, Meyer RG, von Stebut E. Immunohistochemical markers for histopathological diagnosis and differentiation of acute cutaneous graft-versus-host disease. Exp Dermatol 2021; 30:1814-1819. [PMID: 34223669 DOI: 10.1111/exd.14416] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 04/30/2021] [Accepted: 06/07/2021] [Indexed: 11/29/2022]
Abstract
Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4+ and CD8+ T cells. The majority of CD4+ T-helper cells were localized in the upper dermis, whereas cytotoxic CD8+ T cells were found in the epidermis. Increased numbers of CD56+ natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.
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Affiliation(s)
- Joanna Wegner
- Department of Dermatology, University Medical Center Mainz, Mainz, Germany
| | | | - Julia Engelbert
- Department of Dermatology, University Medical Center Mainz, Mainz, Germany
| | - Max Knothe
- Department of Dermatology, University Hospital of Leipzig, Leipzig, Germany
| | - Claudia Braun
- Department of Dermatology, University Medical Center Mainz, Mainz, Germany
| | - Doris Helbig
- Department of Dermatology, University Hospital Cologne and Faculty of Medicine Cologne, University of Cologne, Cologne, Germany
| | - Christopher Sacher
- Department of Dermatology, University Hospital Cologne and Faculty of Medicine Cologne, University of Cologne, Cologne, Germany
| | - Andreas Kreft
- Department of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Eva M Wagner
- Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany
| | - Mirjana Ziemer
- Department of Dermatology, University Hospital of Leipzig, Leipzig, Germany
| | - Ralf G Meyer
- Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany
| | - Esther von Stebut
- Department of Dermatology, University Hospital Cologne and Faculty of Medicine Cologne, University of Cologne, Cologne, Germany
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10
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Yuan J, Zhang Y, Zhang Y, Mo Y, Zhang Q. Effects of metal nanoparticles on tight junction-associated proteins via HIF-1α/miR-29b/MMPs pathway in human epidermal keratinocytes. Part Fibre Toxicol 2021; 18:13. [PMID: 33740985 PMCID: PMC7980342 DOI: 10.1186/s12989-021-00405-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/08/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The increasing use of metal nanoparticles in industry and biomedicine raises the risk for unintentional exposure. The ability of metal nanoparticles to penetrate the skin ranges from stopping at the stratum corneum to passing below the dermis and entering the systemic circulation. Despite the potential health risks associated with skin exposure to metal nanoparticles, the mechanisms underlying the toxicity of metal nanoparticles on skin keratinocytes remain unclear. In this study, we proposed that exposure of human epidermal keratinocytes (HaCaT) to metal nanoparticles, such as nickel nanoparticles, dysregulates tight-junction associated proteins by interacting with the HIF-1α/miR-29b/MMPs axis. METHODS We performed dose-response and time-response studies in HaCaT cells to observe the effects of Nano-Ni or Nano-TiO2 on the expression and activity of MMP-2 and MMP-9, and on the expression of tight junction-associated proteins, TIMP-1, TIMP-2, miR-29b, and HIF-1α. In the dose-response studies, cells were exposed to 0, 10, or 20 μg/mL of Nano-Ni or Nano-TiO2 for 24 h. In the time-response studies, cells were exposed to 20 μg/mL of Nano-Ni for 12, 24, 48, or 72 h. After treatment, cells were collected to either assess the expression of mRNAs and miR-29b by real-time PCR or to determine the expression of tight junction-associated proteins and HIF-1α nuclear accumulation by Western blot and/or immunofluorescent staining; the conditioned media were collected to evaluate the MMP-2 and MMP-9 activities by gelatin zymography assay. To further investigate the mechanisms underlying Nano-Ni-induced dysregulation of tight junction-associated proteins, we employed a HIF-1α inhibitor, CAY10585, to perturb HIF-1α accumulation in one experiment, and transfected a miR-29b-3p mimic into the HaCaT cells before Nano-Ni exposure in another experiment. Cells and conditioned media were collected, and the expression and activities of MMPs and the expression of tight junction-associated proteins were determined as described above. RESULTS Exposure of HaCaT cells to Nano-Ni resulted in a dose-dependent increase in the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 and the activities of MMP-2 and MMP-9. However, exposure of cells to Nano-TiO2 did not cause these effects. Nano-Ni caused a dose-dependent decrease in the expression of miR-29b and tight junction-associated proteins, such as ZO-1, occludin, and claudin-1, while Nano-TiO2 did not. Nano-Ni also caused a dose-dependent increase in HIF-1α nuclear accumulation. The time-response studies showed that Nano-Ni caused significantly increased expressions of MMP-2 at 24 h, MMP-9 at 12, 24, and 48 h, TIMP-1 from 24 to 72 h, and TIMP-2 from 12 to 72 h post-exposure. The expression of miR-29b and tight junction-associated proteins such as ZO-1, occludin, and claudin-1 decreased as early as 12 h post-exposure, and their levels declined gradually over time. Pretreatment of cells with a HIF-1α inhibitor, CAY10585, abolished Nano-Ni-induced miR-29b down-regulation and MMP-2/9 up-regulation. Introduction of a miR-29b-3p mimic into HaCaT cells by transfection before Nano-Ni exposure ameliorated Nano-Ni-induced increased expression and activity of MMP-2 and MMP-9 and restored Nano-Ni-induced down-regulation of tight junction-associated proteins. CONCLUSION Our study herein demonstrated that exposure of human epidermal keratinocytes to Nano-Ni caused increased HIF-1α nuclear accumulation and increased transcription and activity of MMP-2 and MMP-9 and down-regulation of miR-29b and tight junction-associated proteins. Nano-Ni-induced miR-29b down-regulation was through Nano-Ni-induced HIF-1α nuclear accumulation. Restoration of miR-29b level by miR-29b-3p mimic transfection abolished Nano-Ni-induced MMP-2 and MMP-9 activation and down-regulation of tight junction-associated proteins. In summary, our results demonstrated that Nano-Ni-induced dysregulation of tight junction-associated proteins in skin keratinocytes was via HIF-1α/miR-29b/MMPs pathway.
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Affiliation(s)
- Jiali Yuan
- Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202 USA
| | - Yue Zhang
- Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202 USA
| | - Yuanbao Zhang
- Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202 USA
| | - Yiqun Mo
- Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202 USA
| | - Qunwei Zhang
- Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202 USA
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11
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Mazzoni D, Pool L, Muir J. Pathologically oriented descriptive study of male genital circumcisions across medical and surgical specialties. Int J Dermatol 2020; 60:559-563. [PMID: 33319352 DOI: 10.1111/ijd.15359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 10/27/2020] [Accepted: 11/19/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Circumcision is one of the most frequently performed procedure by clinicians, yet its role and indication in clinical practice lacks consensus and remains unclear. We sought to evaluate a collection of male circumcisions to determine the range of indications, histopathological diagnoses, and type of clinicians associated with circumcision. METHODS We performed a retrospective descriptive cohort study of male patients who received a circumcision reported by one major dermatopathology laboratory between January 2017 and December 2018. Data were extracted from the histological report of the pathologist for each case. Patient age, type of clinician, clinical notes, and histopathological diagnosis were evaluated. RESULTS "/> A total of 406 circumcisions were identified. The median age for circumcision was 36 (IQR 16-61). Boys less than 18 years of age made up 24% (98/406). Histological diagnoses included normal (43/406, 11%), nonspecific inflammation (82/406, 20%), inflammatory conditions (264/406, 65%), infections (9/406, 2.2%), benign neoplasms (5/406, 1.0%), and scar tissue (3/406, 0.7%). The most common diagnosis was balanitis xerotica obliterans (226/406, 56%). Rarely, genital infections and neoplastic lesions were identified. Circumcisions were performed by urologists (289/406, 71.2%), general practitioners (76/406, 18.7%), general surgeons (32/406, 8%), pediatric surgeons (5/406, 1%), and dermatologists (4/406, 1%). The main indications for circumcision were phimosis (110/202, 54%), suspected lichen sclerosus (28/202, 14%), and balanitis (15/202, 7%). CONCLUSION Circumcision was performed for a broad range of genital dermatoses across various medical and surgical specialties. Few studies have described these observations. We discuss the common pathological conditions leading to circumcision and its role in diagnosis and treatment.
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Affiliation(s)
- Daniel Mazzoni
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Louis Pool
- Sullivan Nicolaides Pathology, Brisbane, Queensland, Australia
| | - Jim Muir
- Mater Misericordiae Hospital, Brisbane, Queensland, Australia
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12
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Zeidi M, Chen KL, Patel B, Ravishankar A, Lim R, Werth VP. Increased MxA protein expression and dendritic cells in spongiotic dermatitis differentiates dermatomyositis from eczema in a single-center case-control study. J Cutan Pathol 2020; 48:364-373. [PMID: 32954523 DOI: 10.1111/cup.13880] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 08/11/2020] [Accepted: 09/02/2020] [Indexed: 01/22/2023]
Abstract
BACKGROUND Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of DM patients has skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. In this study, we aimed to (a) identify the percentage of clinically diagnosed DM patients with SD skin biopsies, (b) identify cytokine and cell markers that can help determine if a SD skin biopsy is consistent with DM. METHODS In this case-control study, biopsy specimens from ten DM patients with SD (DM-SD) were compared to specimens from ten healthy controls, ten patients with eczema, and 12 patients with DM with ID (DM-ID). Specimens were stained by immunohistochemistry for MxA, IFN-β, CD11c, and BDCA2. One-way ANOVA with Bonferroni's multiple comparison test was used to compare protein expression between groups. RESULTS Eleven of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-β, CD11c, and BDCA2 protein expression was significantly higher in DM-SD compared to eczema and healthy controls. Expressions of MxA, IFN-β, and BDCA2 were not significantly different between DM-SD and DM-ID. CONCLUSION Increased MxA, IFN-β, CD11c, and BDCA2 protein expression may aid in distinguishing between DM-SD and eczema and warrants further investigation.
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Affiliation(s)
- Majid Zeidi
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Kristen L Chen
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Basil Patel
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Adarsh Ravishankar
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Rachel Lim
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Victoria P Werth
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
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13
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Meibomian Glands or Not? Identification of In Vivo and Ex Vivo Confocal Microscopy Features and Histological Correlates in the Eyelid Margin. J Ophthalmol 2020; 2020:7516286. [PMID: 32676204 PMCID: PMC7345604 DOI: 10.1155/2020/7516286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 05/19/2020] [Indexed: 12/28/2022] Open
Abstract
Purpose In vivo confocal laser scanning microscopy (CLSM) is an emerging diagnostic tool allowing fast and easy microscopic tissue examination. For the diagnostics of pathological eyelid margin lesions, the knowledge of the normal eyelid margin is essential. Methods We examined 18 eyelid margins of healthy humans using the in vivo CLSM device and 10 samples of healthy eyelid margins from donor sites with ex vivo CLSM and compared the findings to the corresponding histological sections of donor sites. Cross-section images of different depths and depths of different skin appendages were measured. Results The depth observed by in vivo CLSM is less than 150 μm into the eyelid. Images of the epidermis and superficial dermis skin, appendages including hair follicle, and sebaceous catheters can be captured associated with histopathology and ex vivo confocal microscopy. In correlation with histopathology, we identified different layers of the eyelid margin, different layers of the epidermis, and skin appendages by ex vivo confocal microscopy. Conclusions The study offers an overview of the in vivo confocal microscopy human eyelid margin characteristics in comparison to the standard histological examination and confirms that in vivo CLSM could not observe the meibomian gland acini structure.
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14
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Cho J, Elyaman SA, Avera SA, Iyamu K. Diffuse Exfoliative Rash with Sepsis and Eosinophilia: A Case of Erythroderma? AMERICAN JOURNAL OF CASE REPORTS 2019; 20:1387-1393. [PMID: 31541072 PMCID: PMC6761706 DOI: 10.12659/ajcr.917427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
<strong>BACKGROUND</strong> Erythroderma is an exfoliative dermatitis that manifests as generalized erythema and scaling that involves 90% of the body surface. If untreated, erythroderma can be fatal because of its metabolic burden and risk of secondary infections. <strong>CASE REPORT</strong> The patient was a 56-year-old male with prior rash attributed to group A Streptococcal cellulitis and discharged on Augmentin, Clindamycin with hydrocortisone cream, and Bactrim, but he had been noncompliant. He was admitted again for rash involving the face, torso, and extremities characterized by diffuse, desquamative, dry scales in morbilliform pattern. The patient was septic with <i>Staphylococcus aureus</i> bacteremia and compromised skin barrier. He was started on vancomycin and switched to Cefazolin IV due to concern for drug reaction. Autoimmune workup included antibodies for anti-Jo-1, anti-dsDNA, anti-centromere, and ANCA. However, only antinuclear antibody and scleroderma antibody were positive. Given the unclear workup results and lack of response to antibiotics, the patient was started on prednisone 60 mg PO and topical Triamcinolone 0.1% cream. A skin biopsy revealed psoriasiform hyperplasia with atypical T cell infiltrate and eosinophils, but negative for T cell gene rearrangement. The rash resolved after day 12 of application of topical Triamcinolone. <strong>CONCLUSIONS</strong> This case is unique in terms of the rarity of erythroderma and the diagnostic challenge given confounding factors such as noncompliance and drug reaction. Serious causes, such as SLE and cutaneous T cell lymphoma, were ruled out. Fortunately, the rash responded well to steroids; however, given the adverse effects of long-term use of topical steroids, the patient will need follow up with Dermatology.
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Affiliation(s)
- Jake Cho
- Graduate Medical Education, University of Central Florida College of Medicine, Orlando, FL, USA.,Internal Medicine Residency Program, HCA Ocala Regional Medical Center, Ocala, FL, USA
| | - Selsabeel A Elyaman
- Graduate Medical Education, University of Central Florida College of Medicine, Orlando, FL, USA.,Internal Medicine Residency Program, HCA Ocala Regional Medical Center, Ocala, FL, USA
| | - Stephen A Avera
- Graduate Medical Education, University of Central Florida College of Medicine, Orlando, FL, USA.,Internal Medicine Residency Program, HCA Ocala Regional Medical Center, Ocala, FL, USA
| | - Kenneth Iyamu
- Graduate Medical Education, University of Central Florida College of Medicine, Orlando, FL, USA.,Faculty of Internal Medicine, HCA Ocala Regional Medical Center, Ocala, FL, USA
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15
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Tadros J, Chastain CA, Tkaczyk E. Colonic and perianal ulceration exhibiting vacuolar interface dermatitis in the setting of HIV. Clin Case Rep 2019; 7:1478-1480. [PMID: 31428371 PMCID: PMC6692980 DOI: 10.1002/ccr3.2222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 04/12/2019] [Accepted: 04/28/2019] [Indexed: 11/25/2022] Open
Abstract
We report a case of noninfectious vacuolar interface dermatitis associated with colonic and perianal ulceration in a patient with acquired immunodeficiency syndrome (AIDS), which responded to immunosuppressive treatment. Our findings suggest that interface dermatitis in the setting of AIDS may warrant further gastrointestinal evaluation and may respond to immunosuppression.
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Affiliation(s)
- Joseph Tadros
- University of Cincinnati College of MedicineCincinnatiOhio
- Present address:
University of MissouriColumbiaMI
| | - Cody A. Chastain
- Division of Infectious DiseasesVanderbilt University Medical CenterNashvilleTennessee
| | - Eric Tkaczyk
- Department of Veterans AffairsTennessee Valley Health System – Dermatology and Research ServicesNashvilleTennessee
- Vanderbilt Dermatology Translational Research Clinic, Vanderbilt University Medical CenterNashvilleTennessee
- Department of Biomedical EngineeringVanderbilt UniversityNashvilleTennessee
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16
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Walsh NM, Kutzner H, Requena L, Cerroni L. Plasmacytic cutaneous pathology: A review. J Cutan Pathol 2019; 46:698-708. [PMID: 31095757 DOI: 10.1111/cup.13499] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 05/02/2019] [Accepted: 05/13/2019] [Indexed: 12/23/2022]
Affiliation(s)
- Noreen M. Walsh
- Department of Pathology, Queen Elizabeth II Health Sciences CenterNova Scotia Health Authority (Central Zone) Halifax Canada
- Department of PathologyDalhousie University Halifax Canada
- Department of MedicineDalhousie University Halifax Canada
| | - Heinz Kutzner
- Dermatopathologie Friedrichshafen Friedrichshafen Germany
| | - Luis Requena
- Dermatology DepartmentFundacion Jimenez Diaz Madrid Spain
| | - Lorenzo Cerroni
- Research Unit of Dermatopathology, Department of DermatologyMedical University of Graz Graz Austria
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17
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Atchley TJ, Smith DM. The first pathological specimen from a rare local reaction after subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol 2019; 123:210-211. [PMID: 31071441 DOI: 10.1016/j.anai.2019.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/24/2019] [Accepted: 04/29/2019] [Indexed: 11/26/2022]
Affiliation(s)
- Taylor J Atchley
- Wilford Hall Ambulatory Surgical Center, Allergy and Immunizations Clinic, JBSA Lackland AFB, Texas.
| | - Derek M Smith
- Wilford Hall Ambulatory Surgical Center, Allergy and Immunizations Clinic, JBSA Lackland AFB, Texas
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18
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Barron AMS, Mantero JC, Ho JD, Nazari B, Horback KL, Bhawan J, Lafyatis R, Lam C, Browning JL. Perivascular Adventitial Fibroblast Specialization Accompanies T Cell Retention in the Inflamed Human Dermis. THE JOURNAL OF IMMUNOLOGY 2018; 202:56-68. [PMID: 30510068 DOI: 10.4049/jimmunol.1801209] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 10/29/2018] [Indexed: 12/12/2022]
Abstract
Perivascular accumulation of lymphocytes can be a prominent histopathologic feature of various human inflammatory skin diseases. Select examples include systemic sclerosis, spongiotic dermatitis, and cutaneous lupus. Although a large body of work has described various aspects of the endothelial and vascular smooth muscle layers in these diseases, the outer adventitial compartment is poorly explored. The goal of the current study was to characterize perivascular adventitial fibroblast states in inflammatory human skin diseases and relate these states to perivascular lymphocyte accumulation. In normal skin, adventitial fibroblasts are distinguished by CD90 expression, and dense perivascular lymphocytic infiltrates are uncommon. In systemic sclerosis, this compartment expands, but lymphocyte infiltrates remain sparse. In contrast, perivascular adventitial fibroblast expression of VCAM1 is upregulated in spongiotic dermatitis and lupus and is associated with a dense perivascular T cell infiltrate. VCAM1 expression marks transitioned fibroblasts that show some resemblance to the reticular stromal cells in secondary lymphoid organs. Expanded adventitial compartments with perivascular infiltrates similar to the human settings were not seen in the inflamed murine dermis. This species difference may hinder the dissection of aspects of perivascular adventitial pathology. The altered perivascular adventitial compartment and its associated reticular network form a niche for lymphocytes and appear to be fundamental in the development of an inflammatory pattern.
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Affiliation(s)
- Alexander M S Barron
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
| | - Julio C Mantero
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
| | - Jonathan D Ho
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Banafsheh Nazari
- Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118
| | - Katharine L Horback
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and
| | - Jag Bhawan
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Robert Lafyatis
- Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118.,Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213
| | - Christina Lam
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Jeffrey L Browning
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118; .,Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118
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19
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Bell DC, Brown SJ. Atopic eczema treatment now and in the future: Targeting the skin barrier and key immune mechanisms in human skin. World J Dermatol 2017; 6:42-51. [DOI: 10.5314/wjd.v6.i3.42] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 03/14/2017] [Accepted: 04/07/2017] [Indexed: 02/06/2023] Open
Abstract
The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin (IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.
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20
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Abstract
Recurrent aphthous stomatitis (RAS) is the most common acute oral ulcerative condition in North America. RAS is divided into a mild, common form, simple aphthosis, and a severe, less common form, complex aphthosis. Aphthosis is a reactive condition. The lesions of RAS can represent the mucosal manifestation of a variety of conditions. These include conditions with oral and genital aphthae such as ulcus vulvae acutum, reactive nonsexually related acute genital ulcers, and Behçet disease. The mouth is the beginning of the gastrointestinal (GI) tract, and the lesions of RAS can be a manifestation of GI diseases such as gluten-sensitive enteropathy, ulcerative colitis, and Crohn disease. Complex aphthosis may also have correctable causes. The clinician should seek these in a careful evaluation. Successful management of both simple and complex aphthosis depends on accurate diagnosis, proper classification, recognition of provocative factors, and the identification of associated diseases. The outlook for patients with both simple and complex aphthosis is positive.
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Affiliation(s)
- Ricky Z Cui
- Department of Dermatology, Mayo Clinic, Rochester, MN
| | - Alison J Bruce
- Department of Dermatology, Mayo Clinic, Jacksonville, FL.
| | - Roy S Rogers
- Department of Dermatology, Mayo Clinic, Scottsdale, AZ
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21
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Tod B, Jordaan HF, Schneider JW. Retrospective Value of Skin Biopsy in Histologically Confirmed Cases of the Perivascular Dermatitis Subgroup of the Inflammatory Dermatoses. Am J Dermatopathol 2016; 38:26-32. [PMID: 26730693 DOI: 10.1097/dad.0000000000000384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Skin biopsy is a commonly used and valuable tool in the diagnosis of diseases of the skin. The inflammatory dermatoses are a subgroup that presents diagnostic difficulties from both a clinical and a histopathological perspective. This study examines a particularly challenging subgroup of the inflammatory dermatoses, that is, perivascular dermatitis. The final conclusions of the histological report of 163 biopsies considered to fall into the perivascular dermatitis group were examined, and the value skin biopsy added in the final diagnosis of each case was evaluated. The 2 most valuable potential outcomes of the histopathological report: consistent with clinical diagnosis with strong evidence of a specific diagnosis and new, unexpected, helpful, specific diagnosis, occurred in 40 reports (24.54%).
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Affiliation(s)
- Bianca Tod
- *Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; and †Division of Anatomical Pathology, Department of Pathology, NHLS Tygerberg, Faculty of Medicine and Health Sciences, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa
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22
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Keeling BH, Gavino ACP, Gavino ACP. Skin Biopsy, the Allergists' Tool: How to Interpret a Report. Curr Allergy Asthma Rep 2015; 15:62. [PMID: 26310278 DOI: 10.1007/s11882-015-0560-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Inflammatory dermatoses are frequently encountered by the allergist, and histologic evaluation achieved through skin biopsy can be of tremendous value clinically. There is no substitute for a thorough history and physical exam; however, the skin biopsy is a simple, in-office procedure with little risk of complication that can provide invaluable information when a diagnosis is uncertain. Histopathologically, many inflammatory eruptions can look similar or overlap, but information provided by the dermatopathologist can help the clinician render or refine the clinical diagnosis and guide management. This review will discuss descriptive elements contained in the pathology report to provide a framework that can be used by the allergist to comfortably and confidently diagnose inflammatory dermatologic conditions.
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Affiliation(s)
- Brett H Keeling
- Department of Dermatology, Dell Medical School, The University of Texas at Austin, 601 E. 15th Street, Austin, TX, 78701, USA,
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23
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Noda S, Suárez-Fariñas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, Peng X, Estrada YD, Nakajima S, Honda T, Shin JU, Lee H, Krueger JG, Lee KH, Kabashima K, Guttman-Yassky E. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol 2015; 136:1254-64. [DOI: 10.1016/j.jaci.2015.08.015] [Citation(s) in RCA: 347] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 08/17/2015] [Accepted: 08/18/2015] [Indexed: 01/05/2023]
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Analysis of skin patch test results and metalloproteinase-2 levels in a patient with contact dermatitis. Postepy Dermatol Alergol 2015; 32:154-61. [PMID: 26161054 PMCID: PMC4495108 DOI: 10.5114/pdia.2014.40979] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 12/10/2013] [Accepted: 01/25/2014] [Indexed: 11/21/2022] Open
Abstract
Introduction The complex course of skin reactions that contact eczema involves is due in part to abnormalities of the extracellular matrix function. Proteins that degrade extracellular matrix components include metalloproteinases (MMP), which are divided into subcategories depending on the chemical structure and substrate specificity. Aim To analyse patch test results in contact dermatitis patients and to assess MMP-2 levels during skin lesion exacerbation and remission. Material and methods Fifty patients suffering from contact eczema were qualified to the study and 20 healthy volunteers as a control group. The study group patients had epidermal skin tests performed with the “European Standard” set. To assess the MMP-2 level in serum, venous blood was drawn, twice from study group patients – during contact dermatitis exacerbation and remission periods – and once from control group patients. Assessment of MMP-2 in serum was done with ELISA immunoassay. To verify the proposed hypotheses, parametric and nonparametric significance tests were used. Results Hands were the most frequent location of contact dermatitis. Nickel (II) sulphate was the most frequent sensitizing substance. Mean MMP-2 levels were statistically higher in the study group both in contact dermatitis exacerbation and remission periods than in the control group. There was no statistically significant difference between MMP-2 levels and skin patch test results. Conclusions Nickel is one of the most allergenic contact allergens in patients with contact dermatitis. Metalloproteinase-2 is a good marker of contact dermatitis in various stages of the disease.
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Evaluation of clinico-epidemiological and histopathological features of pityriasis rosea. Postepy Dermatol Alergol 2014; 31:216-21. [PMID: 25254006 PMCID: PMC4171665 DOI: 10.5114/pdia.2014.40641] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Revised: 12/08/2013] [Accepted: 01/06/2014] [Indexed: 11/29/2022] Open
Abstract
Introduction Pityriasis rosea is a sudden-onset and self limiting disease with specific skin rash. The exact etiology is still not clear. Aim To determine epidemiological, etiological, clinical and histopathological features in pityriasis rosea (PR). Material and methods Fifty two patients (older than 18 years) with PR were included in this study. Patients were examined for epidemiological and etiological features. Biopsy specimens obtained from secondary eruptions were histopathologically evaluated with hematoxylin-eosine and immunohistochemically evaluated with CD3 and CD20 monoclonal antibodies. Results Age range of patients was 18–53, mean age was 29.3 ±9.5 and women-to-men ratio was 1.08/1. Thirty-nine (75%) patients had a history of wearing new clothes, 27 (51.9%) patients had a history of recent respiratory tract infection, 15 (28.8%) patients had a history of recent gastrointestinal infection. Eczematous changes were detected in biopsy materials by histopathological evaluation, and cellular infiltrate was positively stained with pan T-cell marker CD3 and negatively stained with B lymphocyte marker CD20 in all biopsy materials in immunohistochemical examination. Conclusions In our study, frequency of pre-disease infection and prodromal symptoms history were determined to be higher than the results of similar studies in the literature. These higher results suggest that PR may be delayed-type hypersensitivity to an infectious factor. However, positive staining of all biopsy materials with pan T lymphocyte marker CD3 supports the association with cellular immunity. We believe that more extensive studies are needed on this issue.
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Youssefi MR, Ebrahimpour S, Rezaei M, Ahmadpour E, Rakhshanpour A, Rahimi MT. Dermatitis caused by Ctenocephalides felis (cat flea) in human. CASPIAN JOURNAL OF INTERNAL MEDICINE 2014; 5:248-50. [PMID: 25489439 PMCID: PMC4247491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 07/04/2014] [Accepted: 07/07/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND Human infestation to ectoparasites such as ticks, lice, cimex, fleas, mites and others agents may result in intensive allergic reaction with symptoms of itching, skin infection and severe irritation. In this case report, we present a case of dermatitis caused by cat flea. CASE PRESENTATION A three-member family referred to dermatology clinic in Babol due to dermal complications. They complained of irritation and the unrest caused by intense itching. Samples of tiny live insects were detected from their clothing which was recognized as C. felis (cat flea). CONCLUSION This report highlights the importance of ectoparasites causing dermatitis.
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Affiliation(s)
| | - Soheil Ebrahimpour
- Infectious Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol ,Iran
| | - Mojtaba Rezaei
- Young Researchers Club, Islamic Azad University, Babol Branch, Iran
| | - Ehsan Ahmadpour
- Department of Medical Parasitology and Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Arash Rakhshanpour
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Lim GS, Kim HN, Kim BB, Kim DH, Kim YS, Kim HS. A Case of Psoriasiform Dermatitis Followed by Tumor Necrosis Factor Inhibitor Treated with Phototherapy. JOURNAL OF RHEUMATIC DISEASES 2013. [DOI: 10.4078/jrd.2013.20.4.270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Gyun Seop Lim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Hyung Nam Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Bo-Bae Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Dong Hyun Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Yun Sung Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Hyun-Sook Kim
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
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Aslan C, Gktay F, Mansur AT, Aydngz KE, Gne P, Ekmeki TR. Clinicopathological consistency in skin disorders: A retrospective study of 3949 pathological reports. J Am Acad Dermatol 2012; 66:393-400. [DOI: 10.1016/j.jaad.2010.12.031] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Revised: 12/27/2010] [Accepted: 12/28/2010] [Indexed: 12/21/2022]
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