Lisa E. Maier

IL-1F5, -F6, -F8, and -F9: A novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression

IL-1F6, IL-1F8, and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control, uninvolved psoriasis, and psoriasis plaque skin using quantitative RT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2 to 3 orders of magnitude in psoriasis plaque versus uninvolved psoriasis skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8, and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8, and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of antimicrobial peptides and matrix metalloproteinases by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of human β-defensin (HBD)-2, HBD-3, and CAMP and protein secretion of HBD-2 and HBD-3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.

Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24

Background Psoriasis is a Th17/Th1‐mediated skin disease that often responds to antitumour necrosis factor (TNF)‐α therapies, such as etanercept.

Hand dermatitis: a focus on allergic contact dermatitis to biocides.

Hand dermatitis is a common disease of the skin resulting in significantly decreased quality of life. Allergic contact dermatitis is a frequent cause of hand dermatitis. Recent studies have revealed that biocides used as preservatives are frequent allergens affecting the hands. This article reviews common biocides implicated in hand dermatitis.

Clinical, Histologic, and Molecular Analysis of Differences Between Erythematotelangiectatic Rosacea and Telangiectatic Photoaging

IMPORTANCE Facial erythema and telangiectasia are commonly associated with the erythematotelangiectatic subtype of rosacea (ETR). It is important for clinicians to recognize that these findings can also be associated with a subtype of photoaging, which we term telangiectatic photoaging (TP). OBJECTIVE To demonstrate that ETR and TP are distinct dermatologic disorders. DESIGN A case-control observational study comparing clinical, histologic, and gene expression features of 26 participants with ETR, 20 with TP, and 11 age- and sex-matched controls in the Program for Clinical Research in Dermatology at University of Michigan. MAIN OUTCOMES AND MEASURES Findings of clinical history and examination, light and electron microscopy, immunohistochemical analyses, and real-time quantitative reverse-transcriptase polymerase chain reaction gene expression. RESULTS Transient erythema was greater in the ETR group (38% graded moderate to severe) than in the TP (0%; P < .001) and control groups (0%; P = .002). Nontransient erythema was also greater in the ETR group (50% graded moderate to severe) than in the TP (25%; P = .03) and control groups (0%; P < .001). Participants with ETR tended to have erythema and telangiectasia primarily on the central face (79%), whereas those with TP tended to have more lateral involvement (57%; P < .001). Those with ETR had significantly less clinical evidence of photodamage (0% graded 6-8 on a photonumeric scale) than those with TP (40% graded 6-8; P = .01). Histologically, there was less evidence of photodamage in ETR than in TP, which had wispy collagen and solar elastosis surrounding blood vessels. Immunohistologic analysis demonstrated greater geometric mean immunostained area by mast cell tryptase staining in ETR samples (0.018%) than in TP (0.004%; P = .01) or control samples (0.001%; P < .001) but no increase in mast cell number, indicative of greater mast cell degranulation. Gene expression of matrix metalloproteinase-3 was 4-fold greater in ETR samples than in TP samples (P = .004) and 5-fold higher than in control samples (P = .004). Gene expression of the neuropeptides calcitonin gene-related peptide (CGRP-α) and substance P was significantly increased in ETR compared with TP (9-fold [P < .001] and 5-fold [P = .002], respectively) and control samples (10-fold [P < .001] and 28-fold [P < .001], respectively). CONCLUSIONS AND RELEVANCE Telangiectatic photoaging is characterized by less transient and nontransient erythema, a more lateral distribution of erythema and telangiectasia, less neurogenic mast cell activation, and less MMP-mediated matrix remodeling than ETR. These data demonstrate that TP is a distinct clinical entity from ETR that can be distinguished on the basis of clinical, histologic, and gene expression findings.

Case series of volar juvenile xanthogranuloma: Clinical observation of a peripheral rim of hyperkeratosis

Juvenile xanthogranuloma is a benign histiocytic tumor predominantly occurring in children as yellowish papules on the head and trunk. Presentations on the volar surfaces are rare and may cause diagnostic confusion with pyogenic granuloma, eccrine poroma and digital fibrokeratoma. We report two patients with unusual presentations of solitary juvenile xanthogranuloma on the palm or sole. Both had lesions lacking the classic yellowish color and demonstrating a well‐defined, peripheral hyperkeratotic rim. Histopathological evaluation revealed prominent orthokeratosis corresponding to the rim. Additional histological features, including dermal histiocytes and Touton giant cells, were consistent with the diagnosis of juvenile xanthogranuloma. Given the unusual locations and colors of the lesions, we conclude that histopathological evaluation is central to diagnosing volar juvenile xanthogranuloma. We additionally suggest that juvenile xanthogranuloma should be included in the differential diagnoses of volar lesions displaying a peripheral hyperkeratotic rim.

Chapter 24 – Photocontact Dermatitis

Publisher Summary This chapter focuses on photoallergy and phototoxicity and lists some relevant compounds responsible for these distinct entities. It explains the clinical workup of photosensitive patients, including phototesting, and discusses management strategies for photosensitivity and photoallergy. Photocontact dermatitis results from skin exposure to an endogenous or exogenous offending substance, and skin exposure to UV radiation worsens the condition. Photosensitivity is an abnormal cutaneous reaction to solar ultraviolet radiation. This reaction may clinically manifest as a greater propensity toward sunburn or development of a rash upon exposure to solar radiation. A variety of etiologies may be responsible, including porphyria, connective tissue disease, nutritional abnormalities, genetic diseases, and idiopathic disorders. Phototoxic reactions are the most common type of exogenous photosensitivity. This is a nonimmune-mediated mechanism of photosensitivity that may occur in any individual. In these reactions, an offending chemical absorbs UVR and becomes activated; this activated chemical then causes direct tissue damage. Pesticides such as chlorothalonil can cause phototoxic or photoallergic reactions. Until dermatotoxicologic assays are done for many of the suspect agricultural chemicals; however, the field of dermatology will misdiagnose or completely miss the diagnosis of many photocontact dermatoses. Therefore, dermatotoxicologic characterization and identification are of the essence to susceptible individuals because photocontact dermatoses often resolve upon avoidance of the offending agent.

Chapter 23 – Irritant Dermatitis

Publisher Summary This chapter discusses the factors influencing irritant potential, delineates general clinical presentations of irritant dermatitis, and addresses workup and treatment. In addition, it addresses methods of evaluating a chemicals irritant potential and discusses the irritation potential of some agricultural chemicals and plants. Irritant contact dermatitis (ICD) is defined as nonimmunologic skin inflammation after contact to a substance or physical factor. Although epidemiologic data are scarce, ICD appears to be an important cause of occupational and nonoccupational skin disease. Various factors influence a chemicals irritant potential. Intrinsic molecular properties such as molecular structure, size, ionization state, lipid solubility, and pKa determine the chemicals interaction with the skin barrier and epidermal cells. Irritant potential is also dependent on the molar concentration and volume and duration of the exposure. Physical factors such as extremes of temperature and humidity, as well as mechanical factors such as occlusion and friction, can enhance irritation of chemicals or act as irritants. Endogenous factors such as age, anatomical site, preexisting dermatologic conditions, and genetic background may influence an individuals predisposition to irritant dermatitis. There is a decreased susceptibility of irritation with increasing age, with children younger than 8 years being most susceptible to skin irritation. Few human studies exist, and new studies are currently inhibited by the U.S. Environmental Protection Agencys ethics system. Lastly, epidemiologic data that are so helpful for many contact allergens remain scarce for agricultural irritants. The techniques and assays are efficient; however, a regulatory system that promotes developing and registering relevant data in this arena is lacking.