Sharon E. Jacob

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity.

BACKGROUND: Psoriatic plaques have been shown to contain increased levels of proinflammatory cytokines. Serum levels of interleukin (IL)-6, IL-7, IL-8, and interferon (IFN)-gamma have been reported elevated in psoriatic patients. AIM: To evaluate serum cytokine profiles in psoriasis patients by improved enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. METHODS: We analyzed single serum samples from 10 patients with active untreated psoriasis, two patients with active treated psoriasis, and five healthy volunteers for major T helper type 1 and T helper type 2 cytokines using the LINCOplex ELISA multi-analyte detection system that permits simultaneous detection of multiple cytokines from a single sample. The disease severity, including erythema, induration, scale, and surface area, was assessed. RESULTS: IFN-gamma was markedly elevated in all sera from psoriasis patients, 33.8 +/- 1.3 pg/ml (mean +/- standard error) versus 8 +/- 1.5 pg/ml for normal controls (p < 0.01), and positively correlated with all indices of disease severity (Spearman r > 0.6). IL-8 was also increased in psoriasis patients (24.4 +/- 1.8 pg/ml) versus normal controls (3.6 +/- 1.2 pg/ml) (p < 0.05) and positively correlated with the degree of erythema (Spearman r > 0.6). Mean IL-12 levels were decreased in sera from psoriasis patients (8.5 +/- 1.2 pg/ml) compared with normal controls (42.2 +/- 5.3 pg/ml) (p < 0.01). Also, serum IL-10 levels were below detection levels in psoriatics compared with controls (6.4 +/- 1.3 pg/ml). CONCLUSIONS: This new ELISA system allowed rapid and reliable detection of numerous cytokines in single serum samples from patients with psoriasis. We observed that IFN-gamma and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased.

Systemic Contact Dermatitis

Systemic contact dermatitis (SCD) describes a cutaneous eruption in response to systemic exposure to an allergen. The exact pathologic mechanism remains uncertain. The broad spectrum of presentations that are often nonspecific can make it difficult for the clinician to suspect this disease, but it is an important diagnosis to consider in cases of recalcitrant, widespread, or recurrent dermatitis, in which patch testing often reveals allergy to nickel or balsam of Peru. Diagnosis and appropriate management can be life-altering for affected patients. This article on SCD provides an overview of the disease with descriptions of common allergens and some insight into the possible mechanism of action seen in SCD.

Topical application of imiquimod 5% cream to keloids alters expression genes associated with apoptosis

Keloids are benign mesenchymal tumours, usually present at and extending beyond the margins of sites of previous injury. It is reported that keloids display aberrant expression of apoptotic genes: TGFB1 is activated, whereas caspase 8 and 3 are not, thus indicating a block upstream in the apoptosis cascade in keloids. Interferon‐α2b normalizes the excessive synthesis of collagen, glycosaminoglycans and collagenase by keloidal fibroblasts, reduces recurrences following keloid excision, and enhances the expression of native p53 and apoptosis. Imiquimod, a rapid and potent inducer of interferons locally at the site of application to the skin, reduces recurrences following keloid excision and alters gene expression of markers of apoptosis in basal cell carcinoma cells. We investigated the effects with respect to the expression of apoptotic genes in keloidal tissue compared with nontreated controls of imiquimod 5% cream applied topically to keloids. Total RNA was extracted from excised keloidal tissue, cDNA probes synthesized and then hybridized to gene‐specific cDNA fragments spotted on membranes. The expression levels of 96 genes involved in apoptosis, relative to cyclophilin expression, were compared in the imiquimod‐treated and untreated groups. The mean ratio of expression, relative to cyclophilin of caspase 3 and DFFA were significantly enhanced. Caspase 3 was significantly downregulated and DFFA was significantly upregulated in the group of imiquimod‐treated keloids (P < 0·05) compared with the untreated group of keloids. Although imiquimod is capable of altering the expression of these markers of apoptosis in keloids, their role, if any, in the therapeutic response of keloids to imiquimod requires further investigation.

Allergic contact dermatitis in children: common allergens and treatment: a review.

Purpose of review The following study reviews the recent literature pertaining to allergic contact dermatitis (ACD) in the pediatric population. This study also provides an overview of the most common allergens and discusses various therapeutic modalities. Recent findings The pathophysiology of ACD is intricate and multifaceted, resulting in a characteristic, delayed inflammatory response. Although commonly recognized in adults, its existence in the pediatric population was questioned. Recent literature suggests that pediatric ACD exists and is more common than previously recognized. The diagnosis relies on the clinical presentation combined with appropriate use and interpretation of a patch test. Although many studies have investigated ACD in children, few have documented the relevance of positive patch test reactions until recently. The most current prevalence estimates of positive patch test reactions range from 14 to 70% of children patch tested. Although that range is broad, these studies have demonstrated the relevance of positive reactions and confirmed ACD as a disease entity in children. Summary ACD is a previously underrecognized disease process in the pediatric population that can manifest as a serious dermatologic challenge for both patients and physicians. This review will address the prevalence, diagnostic methods, frequent allergens and treatment options in pediatric ACD.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

IMPORTANCE Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00847912.

Contact Allergy: alternatives for the 2007 North American contact dermatitis group (NACDG) Standard Screening Tray.

ost primary care physicians see a large number of patients each year ith eczematous skin diseases. Although many of these patients have topic eczema, another extremely common cause of eczema is contact llergy. This subgroup of eczema patients is notably resistant to treatment nless the causative allergens can be identified and eliminated. It is stimated that allergic contact dermatitis (ACD) to topical products alone ccurs in 1% to 3% of the general population. Unlike respiratory and ood allergies, ACD is not histamine-mediated but is instead a T-cellediated delayed-type hypersensitivity reaction. The basic pathophysilogic process behind ACD is primary skin contact with an allergenic hemical which triggers an immune cascade and results in an eczematous eaction at the site of contact. On first exposure to low molecular weight chemical substances (haptens 500 Da), there is generally no skin reaction. During this first phase, hese haptens enter the epidermis and are recognized by antigen presentng cells, which in turn create signals that transform naive T cells into emory T cells, a process which typically takes 5 to 25 days. ubsequent reactions due to “challenge” with the same chemical subtance generally occur between 24 and 48 hours after exposure; however, eports of reactions occurring as early as 8 hours after exposure and as ong as 1 week after exposure are not uncommon.

Systemic Contact Dermatitis in Children: How an Avoidance Diet Can Make a Difference

Abstract:  Systemic contact dermatitis is an under‐recognized skin reaction that occurs secondary to systemic (oral, intravenous, intramuscular, inhaled, or subcutaneous) exposure to a hapten in a previously sensitized individual. Medicaments are the most common cause of SCD in the adult population, but other chemicals like nickel, cobalt, balsam of Peru, and formaldehyde have been implicated as well. Few reports in children exist to date. Dietary restriction has shown to be of some benefit in managing some adult patients. We present a case series of 8 pediatric patients diagnosed with SCD from the contact dermatology clinic, who showed marked improvement of their dermatitis after adequate dietary avoidance. We review common presentations of chemicals causing SCD in children and potential dietary modifications.

Nickel allergy in the United States: A public health issue in need of a “nickel directive”

To the Editor: Once thought to be rare in the pediatric population, allergic contact dermatitis is now recognized as a significant problem, and nickel has received much attention for being the most commonly sensitizing agent. Nickel sensitization among pediatric patients is well known, but recently it has become apparent that the prevalence is on the rise. The alarming frequency of sensitization to nickel—especially in women and children—led to nickel being named the 2008 ‘‘Allergen of the Year’’ by the American Contact Dermatitis Society. Galvanization eczema (nickel contact allergy) historically referred to the presentation of severe hand dermatitis in miners and electroplating manufacturers. Today, however, patients with nickel contact allergy present with a range of reactions, from localized dermatitis, classically located in the periumbilical area or on the earlobes (relating to repeated contact with clothing snaps and jewelry, respectively), to a severe and debilitating systemic dermatitis. Studies demonstrating that females are more frequently affected suggests a likely relationship with early age exposure to nickel during ear piercing practices. Nickel is ubiquitous in our environment, and exposure is difficult to prevent. Because it is durable and alloys easily with other metals, it is widely used, being present in many commonly encountered objects from zippers, paper clips, and belt buckles to jewelry, keys, and cell phones. In addition, higher plants extract nickel from the soil and use it as a cofactor in growth and metabolism. Food, therefore, is a source of environmental nickel exposure and can be of importance in the management of nickel allergic contact dermatitis. Some complementary and alternative remedies also contain high levels of nickel. Nickel can also be found in several multivitamins, including Centrum and One-a-Day Maximum, as well as in various generics such Rite Aid Whole Source Multivitamin and Kirkland Signature Daily Multivitamin. In addition, nickel and metal allergy may play a role in hypersensitivity reactions associated with endovascular, orthopedic, and dental devices, and dermatologists and allergists are increasingly being consulted about the risk of allergic reactions from inserting these devices. The ubiquitous presence of nickel and nickel-containing alloys in our environment makes frequent

Cutaneous Wegener's granulomatosis (malignant pyoderma) in a patient with Crohn's disease

We report a case of an unusual presentation of Wegeners granulomatosis (WG) in a patient with Crohns disease (CD). She presented to our Wound Care Center with 7th cranial nerve palsy and facial pyoderma‐like ulcerations. Although WG has a predilection for the lung, kidney, and eyes, cutaneous involvement can be seen in 50% of the cases, and it can be the presenting sign in 9–14%. Because of the lethality of WG if not properly treated, the diagnosis is imperative.

Methylisothiazolinone: a case of perianal dermatitis caused by wet wipes and review of an emerging pediatric allergen.

Methylisothiazolinone (MI) is a preservative found in cosmetic, personal hygiene, and industrial products. It has been characterized as a moderate to strong sensitizer and is an emerging allergen in the pediatric population. We discuss a case of perianal dermatitis in a child caused by contact allergy to MI‐containing wet wipes.