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Dermatologic Aspects of Sulfur Mustard Exposure

  • Masoud Maleki
  • Pouran LayeghEmail author
Chapter

Abstract

The skin is one of the important affected target organs by sulfur mustard (SM) as a chemical weapon, besides the eyes and lungs. Skin exposure with sulfur mustard results in the onset of a multiple series of events including a full set of dermal responses for normal wound healing and their mutual influence on each other, eventually leading to skin toxicity. In this process, various mediators that have a regulating role in inflammation, apoptosis, immune responses and some signaling pathways are involved. In this chapter we try to describe the current knowledge on the potential mechanisms which mediate the SM actions on skin, the clinical manifestations in the acute phase of exposure and years later (delayed or chronic ones), histopathology of SM-exposed skin and the potential therapeutic countermeasures.

Keywords

Chemical weapons Alkylating agents Sulfur mustard Cutaneous toxicity Skin Adjunct therapy 

Notes

Glossary

AP-1

Activator Proein-1: a transcription factor which regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections.

Blister (bullae):

Elevated, circumscribed lesion, >1 cm in diameter primarily filled with clear fluid.

CAM

Calcium Modulated Protein: a calcium-binding messenger protein, a multifunctional intermediate messenger protein that transduces calcium signals by binding calcium ions and then modifying its interactions with various target proteins.

Desmosome:

A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material.

Dyskeratosis:

Abnormal keratinization occurring prematurely within individual cells or groups of cells below the stratum granulosum.

e NOS:

endothelial Nitrogen Oxide Synthases.

ECM

Extra Cellular Matrix: a collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells.

Eczema:

A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents.

Epidermis:

The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).

Erosion:

Partial loss of epidermis (epithelium).

Erythema:

Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes.

Eschar:

A slough or piece of dead tissue that is cast off from the surface of the skin, particularly after a burn injury, but also seen in gangrene, ulcer, fungal infection.

Hemidesmosome:

An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins.

Hypodense:

Abnormality which is less dense than the reference structure.

IL

Interlukin: a group of cytokines (secreted proteins and signaling molecules) that were first seen to be expressed by white blood cells.

INFγ

Interferonγ: a dimerized soluble cytokine that is the only member of the type II class of interferons.

iNOS:

inducible Nitrogen Oxide Synthases.

LD50

Lethal Dose, 50 %: The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50 % of the tested population.

MAPK

Mitogen-activated protein kinases (MAPK): A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases, which in turn are activated by mitogen-activated protein kinase kinase kinases.

Melanophage:

A histiocyte that contains phagocytized melanin.

MMP

Matrix Metalloproteinases (MMPs): zinc-dependent endopeptidases that are capable of degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules.

n NOS:

neural Nitrogen Oxide Synthases.

NAD+

Nicotinamide adenine dinucleotide: A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH).

NF-KB

Nuclear factor kappa-light-chain-enhancer of activated B cells: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli.

Nikolsky sign:

A skin finding in which the top layers of the skin slip away from the lower layers when slightly rubbed.

NOSs

Nitrogen Oxide Synthases: a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule.

NSAIDs

Non-steroidal Anti-inflammatory Drugs: a class of drugs that provides analgesic and antipyretic effects, and, in higher doses, anti-inflammatory effects.

Papillary dermis:

Is the uppermost layer of the dermis. It intertwines with the rete ridges of the epidermis and is composed of fine and loosely arranged collagen fibers.

Papule:

Elevated, circumscribed lesion, <1 cm in diameter which its elevation is due to increased thickness of the epidermis and/or cells or deposition within the dermis.

PARPs

Poly (ADP-ribose) polymerase: a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death.

Poikiloderma:

A skin condition that consists of areas of hypopigmentation, hyperpigmentation, telangiectasias and atrophy.

Pyknosis or karyopyknosis:

The irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.

RNS

Reactive Nitrogen Species: a family of antimicrobial molecules derived from nitric oxide (NO) and superoxide (O2 · −) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively.

ROS

Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids.

RSDL

Reactive Skin Decontamination Lotion: a proposed replacement for the existing skin and equipment decontamination kit.

Scar:

Areas of fibrous tissue (fibrosis) that replace normal skin after injury.

SM

Sulfur mustard: a class of related cytotoxic and vesicant chemical warfare agents with the ability to form large blisters on the exposed skin and in the lungs.

Spinousum cell:

One of the layers of the epidermis, composed of several layers of polygonal cells. It lies on top of the stratum basale and beneath the stratum granulosum.

TEWL

Trans Epidermal Water Loss: The quantity of water that passes from inside a body (animal or plant) through the epidermal layer to the surrounding atmosphere via diffusion and evaporation processes.

TNFα

Tumor Necrosis Factor α, cachexin, or cachectin): a cell signaling protein involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.

Ulcer:

Full-thickness loss of epithelium (epidermis).

Vesicle:

Elevated, circumscribed lesion, <1 cm in diameter primarily filled with clear fluid.

Xerosis:

The medical term for abnormally dry skin. This name comes from the Greek word “xero,” which means dry.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Dermatology DepartmentCutaneous Leishmaniasis Research Center, Mashhad University of Medical SciencesMashhadIran
  2. 2.Emam Reza HospitalMashhadIran
  3. 3.Ghaem HospitalMashhadIran

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