Multilevel symmetric neuropathic pruritus (MSNP) presenting as recalcitrant "generalized" pruritus.

BACKGROUND: Chronic itch is a disruptive and disabling condition that can lead to psychological stress and depression. OBJECTIVE: We sought to describe an entity of generalized, symmetric, neuropathic pruritus, which we term "multilevel symmetric neuropathic pruritus," and offer possible explanations accounting for its pathogenesis. METHODS: A case series of 14 patients was evaluated at academic institutions from 2011 to 2015. RESULTS: All patients exhibited detectable degenerative vertebral changes, as seen by spinal x-ray or magnetic resonance imaging. In 12 of 14 (85.7%) subjects, the radiographic imaging abnormalities directly correlated with the distribution of their cutaneous findings. Twelve of 14 (85.7%) patients had cutaneous findings along the C5 to C6 and/or C6 to C7 dermatomal distributions. Eleven of 14 (78.5%) patients were overweight or obese, and 14 of 14 (100%) patients had at least 4 risk factors for the development of atherosclerosis. Twelve of 14 (85.7%) patients noted complete or near complete resolution after treatment with gabapentin (300-1200 mg daily). LIMITATIONS: No healthy age-matched control group without pruritus was investigated. CONCLUSION: A combination of multilevel degenerative disc disease of the spine, spinal nerve root impingement, and/or nerve root traction may play a pivotal role in the cause of multilevel symmetric neuropathic pruritus.

Pediatric Positional Sitting Dermatitis: A New Form of Pediatric Contact Dermatitis.

We report on four pediatric patients who presented with localized dermatitis in areas subject to repetitive friction due to their sitting positions. We propose that the cause of the eruption was irritant contact dermatitis due to frequently sitting in a crossed-leg sitting position, an entity for which we have coined the term pediatric positional sitting dermatitis (PPSD). The goal of this report is to raise clinicians' awareness of PPSD, which to our knowledge has not been previously described, and to discuss management of these patients.

Voriconazole-Induced Subacute Cutaneous Lupus Erythematosus in an Adult With Aspergillosis.

A 59-year-old man was treated with voriconazole for chronic invasive aspergillosis and who subsequently developed subacute cutaneous lupus erythematosus (SCLE). The patient presented with a 6-week history of multiple erythematous papulosquamous lesions on his chest, upper and lower extremities, and back (Figure 1). They were nonpruritic and nonpainful. He was afebrile and otherwise well. He had no history of extensive sun exposure prior to the appearance of the eruption. He had been taking voriconazole for about 3 months prior to the onset of lesions. He denied any family history of connective tissue disease.

Fibroblast senescence and squamous cell carcinoma: how wounding therapies could be protective.

BACKGROUND: Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease, with the majority of these cancers diagnosed in people age 70 and older. Recent findings have led to a new hypothesis on the pathogenesis of SCC. OBJECTIVES: To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. MATERIALS AND METHODS: Survey of current literature on wounding therapies to prevent SCCs. RESULTS: This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in the dermis, resulting in a reduction in dermal insulin-like growth factor-1 (IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress ultraviolet light B (UVB)-induced mutations, leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, protecting geriatric keratinocytes from UVB-induced SCC initiation. CONCLUSIONS: In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC.

Fluorescence in situ hybridization (FISH) as an aid for the diagnosis of graft-versus-host disease in two multivisceral organ transplant patients.

We herein describe 2 cases of adult multivisceral transplant patients who developed graft-versus-host disease manifesting predominantly as lichenoid skin papules and plaques. The diagnosis was supported by histopathology but ultimately corroborated by the utilization of the fluorescence in situ hybridization (FISH) technique using X and Y chromosome probes on unstained biopsy slides. In both cases, FISH revealed a high percentage of donor-derived cells as part of the inflammatory infiltrate in the skin biopsy. This report adds to the previous publications showing the utility of FISH in corroborating the diagnosis of graft-versus-host disease in transplant patients with unmatched sex donor.

Treatment outcomes of secondarily impetiginized pediatric atopic dermatitis lesions and the role of oral antibiotics.

Patients with atopic dermatitis (AD) are predisposed to infection with Staphylococcus aureus, which worsens their skin disease; it has been postulated that the lack of antimicrobial peptides due to aberrant allergic inflammation in skin with AD could mediate this enhanced bacterial susceptibility. We sought to characterize the amounts of S. aureus and biological products found in infected AD lesions and whether treatment with topical corticosteroids and oral cephalexin as the only antimicrobial improved outcomes. Fifty-nine children with clinically and S. aureus-positive impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index, and wash fluid was obtained from the lesion for quantitative bacterial culture and antibiotic sensitivities and measurement of bacterial products and cytokines. Subjects were re-evaluated 2 weeks after treatment. Improvement in the clinical and inflammatory characteristics of impetiginized lesions were noted, even in the 15% of lesions infected with Methicillin-resistant S. aureus (MRSA). In a subgroup of subjects whose lesions did not contain S. aureus 2 weeks after initiating treatment, beta-defensin levels were higher at both visits than in normal skin. Treatment of uncomplicated impetiginized pediatric AD with topical corticosteroids and cephalexin results in significant clinical improvement, even in subjects infected with MRSA. We propose that the inhibition of abnormal inflammation by the treatment regimen, resulting in the high levels of defensins, is involved in the improvement of AD and that systemic antibiotics do not appear to be necessary in secondary impetiginized AD.

Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid.

BACKGROUND: Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown. OBJECTIVE: We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions. METHODS: Eighty-nine children with clinically impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically by using the Eczema Area and Severity Index (EASI), wash fluid obtained from the lesion for quantitative bacterial culture, and measurement of LTA and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities. The patients were treated with a regimen that included topical corticosteroids and systemic antibiotics, and the lesion was reanalyzed after 2 weeks. RESULTS: S aureus was identified in 79 of 89 children enrolled in the study. The bacterial colony-forming unit (CFU) counts correlated with the EASI lesional score (P = .04). LTA levels as high as 9.8 mug/mL were measured in the wash fluid samples, and the amounts correlated with the lesional EASI scores (P = .01) and S aureus CFU (P < .001). Approximately 30% of clinically impetiginized AD lesions contained greater than 1 mug/mL LTA, amounts that exert effects on various cell types in vitro. Moreover, injection of skin tissue ex vivo with amounts of LTA found in AD lesions resulted in epidermal cytokine gene expression. CONCLUSION: Pharmacologic levels of LTA are found in many infected atopic dermatitis lesions.

Inter- and Intra-physician variation in quantifying actinic keratosis skin photodamage.

We investigated the variations in physician evaluation of skin photodamage based on a published photodamage scale. Of interest is the utility of a 10-level scale ranging from none and mild photodamage to actinic keratosis (AK). The dorsal forearms of 55 adult subjects with various amounts of photodamage were considered. Each forearm was independently evaluated by 15 board-certified dermatologists according to the Global Assessment Severity Scale ranging from 0 (less severe) to 9 (the most progressed stage of skin damage). Dermatologists rated the levels of photodamage based upon the photographs in blinded fashion. Results show substantial disagreement amongst the dermatologists on the severity of photodamage. Our results indicate that ratings could be more consistent if using a scale of less levels (5-levels or 3-levels). Ultimately, clinicians can use this knowledge to provide better interpretation of inter-rater evaluations and provide more reliable assessment and frequent monitoring of high-risk populations.

Scratching the surface: towards understanding the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10%-20% of infants and 1%-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. At least half of the children with AD develop some other form of atopic disease later in life. The pathogenesis of AD involves a complex interplay of factors, including genetic predisposition due to altered immune or skin barrier function, interactions with the environment, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of AD in human and animal model systems. These insights provide new therapeutic potential for the treatment of human AD.

Quantifying skin photodamage with spatial frequency domain imaging: statistical results.

We investigated the change in optical properties and vascular parameters to characterize skin tissue from mild photodamage to actinic keratosis (AK) with comparison to a published photodamage scale. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on the dorsal forearms of 55 adult subjects with various amounts of photodamage. Dermatologists rated the levels of photodamage based upon the photographs in blinded fashion to allow comparison with SFDI data. For characterization of statistical data, we used artificial neural networks. Our results indicate that optical and vascular parameters can be used to quantify photodamage and can discriminate between the stages as low, medium, and high grades, with the best performance of ∼70%, ∼76% and 80% for characterization of low- medium- and high-grade lesions, respectively. Ultimately, clinicians can use this noninvasive approach for risk assessment and frequent monitoring of high-risk populations.

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor.

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.

Plantar ulcerative lichen planus: rapid improvement with a novel triple-therapy approach.

Ulcerative lichen planus (ULP) is a rare variant of lichen planus that is characterized by chronic, painful, and disabling ulcerations. Ulcerative lichen planus has been known to be resistant to many treatments, and therapeutic interventions often involve use of aggressive immunosuppressive medications without satisfactory remission of symptoms. We present the case of a 56-year-old man with an 8-year history of painful ulcerations on the right plantar foot as well as a large ulceration of the left lateral tongue. Biopsy confirmed a suspected diagnosis of plantar ULP. The patient developed marked clinical improvement of the cutaneous and oral mucosal lesions with oral and topical steroids, topical tacrolimus, and oral doxycycline after only 4 weeks of treatment. It is important for dermatologists to be aware of the potential diagnosis of plantar ULP, especially in the evaluation of chronic treatment-resistant ulcers that often have been previously misdiagnosed. We introduce this novel therapeutic regimen as a rapidly effective and relatively safe alternative to conventional immunosuppressive agents for long-term management of plantar ULP.

Recalcitrant papulopustular rosacea in an immunocompetent patient responding to combination therapy with oral ivermectin and topical permethrin.

A 68-year-old healthy man presented with papulopustular rosacea (PPR) recalcitrant to multiple therapies, including permethrin cream 5%. Histologic examination detected the presence of chronic folliculitis and numerous Demodex organisms. A diagnosis of rosacealike demodicidosis was rendered, and the patient was treated with oral ivermectin and permethrin cream 5%, resulting in resolution of the folliculitis. Demodex infestation should be considered in any patient with rosacealike dermatitis resistant to conventional rosacea therapies. If infestation is demonstrated in these patients, oral ivermectin in combination with topical permethrin is a safe and effective therapeutic option.

Discrete and Coalescing Pustules Masking Severe Recalcitrant Rosacea Due to Demodex.

CONTEXT: Rosacea is a frequent and often easily treatable condition in dermatological practice. The clinical manifestations of rosacea are hypothesized to be the result of a dysregulation of the innate immune system. The roles played by outside factors, such as the presence of Demodex or localized immunosuppression in the pathogenesis of rosacea, are under considerable debate. OBJECTIVE: The current study intended to examine the contribution of immunosuppression to a case of recalcitrant rosacea and the effects of nutritional status in the resolution of the skin disease. DESIGN: The research team designed a case study. SETTING: The study took place at the dermatology clinic of the Department of Dermatology at Indiana University (Indianapolis, IN, USA). PARTICIPANT: The participant was a 36-y-old male patient at the clinic with a recalcitrant dermatosis of the face and neck. This patient's disease had persisted despite multiple standard treatments for facial dermatitis, rosacea, and granulomatous rosacea with a high Demodex burden. INTERVENTION: The intervention included a tapering course of cyclosporin, 3 mg of ivermectin daily for 3 wk, 500 mg daily of ascorbic acid, 1000 units daily of cholecalciferol, and green smoothies. OUTCOME MEASURES: The study measured the patient's levels of immunoglobulin M (IgM), 25 hydroxyvitamin D, and ascorbic acid. RESULTS: The testing showed isolated IgM deficiency and low levels of 25 hydroxyvitamin D and ascorbic acid. The rash resolved following the tapering course of cyclosporin and vitamin repletion through supplements and dietary alteration. CONCLUSIONS: The case was one with multiple confounding variables: (1) the presence of Demodex, (2) iatrogenic immunosuppression due to prolonged systemic and topical steroid use, and (3) vitamin deficiency. The case demonstrates the multifactorial pathogenesis of a recalcitrant dermatosis of the face and neck, and the research team encourages providers to consider a holistic approach when patients do not respond to standard medical therapy.

Pediatric Contact Dermatitis Registry Data on Contact Allergy in Children With Atopic Dermatitis.

Importance: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) have a dynamic relationship not yet fully understood. Investigation has been limited thus far by a paucity of data on the overlap of these disorders in pediatric patients. Objective: To use data from the Pediatric Contact Dermatitis Registry to elucidate the associations and sensitizations among patients with concomitant AD and ACD. Design, Setting, and Participants: This retrospective case review examined 1142 patch test cases of children younger than 18 years, who were registered between January 1, 2015, and December 31, 2015, by 84 health care providers (physicians, nurse practitioners, physician assistants) from across the United States. Data were gathered electronically from multidisciplinary providers within outpatient clinics throughout the United States on pediatric patients (ages 0-18 years). Exposures: All participants were patch-tested to assess sensitizations to various allergens; history of AD was noted by the patch-testing providers. Main Outcomes and Measures: Primary outcomes were sensitization rates to various patch-tested allergens. Results: A total of 1142 patients were evaluated: 189 boys (34.2%) and 363 girls (65.8%) in the AD group and 198 boys (36.1%) and 350 girls (63.9%) in the non-AD group (data on gender identification were missing for 17 patients). Compared with those without AD, patch-tested patients with AD were 1.3 years younger (10.5 vs 11.8 years; P < .001) and had longer history of dermatitis (3.5 vs 1.8 years; P < .001). Patch-tested patients designated as Asian or African American were more likely to have concurrent AD (odds ratio [OR], 1.92; 95% CI, 1.20-3.10; P = .008; and OR, 4.09; 95% CI, 2.70-6.20; P <.001, respectively). Patients with AD with generalized distribution were the most likely to be patch tested (OR, 4.68; 95% CI, 3.50-6.30; P < .001). Patients with AD had different reaction profiles than those without AD, with increased frequency of reactions to cocamidopropyl betaine, wool alcohol, lanolin, tixocortol pivalate, and parthenolide. Patients with AD were also noted to have lower frequency of reaction to methylisothiazolinone, cobalt, and potassium dichromate. Conclusions and Relevance: Children with AD showed significant reaction patterns to allergens notable for their use in skin care preparations. This study adds to the current understanding of AD in ACD, and the continued need to investigate the interplay between these disease processes to optimize care for pediatric patients with these conditions.

Rosacea Fulminans Precipitated by Acute Stress: A Case Report Describing an Integrative Approach for a Patient Reluctant to Use Isotretinoin.

CONTEXT: Rosacea fulminans is a rare skin disorder with a multifactorial etiology. Stress is one of the common precipitating factors of this condition but is not often targeted in treatment. Isotretinoin is considered part of the first-line therapy for this condition but, in cases where its use is restricted, other therapeutic interventions as part of an integrative approach may be effective. PATIENT CONCERNS: A 38-y-old female presented with rosacea fulminans brought on by an acutely stressful event. After multiple failed therapies, she experienced resolution of her symptoms with a combination of systemic corticosteroids, antibiotics, diet modification, and stress reduction, with the treatment of stress playing a significant role. CONCLUSIONS: Stress management and diet modification are key adjunctive therapies in the treatment of rosacea fulminans and need to be addressed more often in treatment. In cases where patients are reluctant or unable to take isotretinoin, an integrative approach may be effective in achieving symptomatic improvement.

Pediatric Contact Dermatitis Registry Inaugural Case Data.

BACKGROUND: Little is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. OBJECTIVE: The aim was to quantify patch test results from providers evaluating US children. METHODS: The study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015-2016). RESULTS: One thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). CONCLUSIONS: This US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

Cutaneous manifestation of α1-antitrypsin deficiency: panniculitis absent on biopsy.

Patients with α1-antitrypsin (AAT) deficiency may develop cutaneous manifestations of the disorder that histologically appear as panniculitis. Algorithms consistently emphasize measuring AAT levels when both clinical and histological features of deficiency are present; however, the patient's medical history and a physical examination alone can be extremely helpful in guiding the physician to the diagnosis of AAT deficiency. We describe a patient who presented with the classic clinical findings of AAT deficiency-associated panniculitis with surprising absence of panniculitis on repeated deep incisional biopsies. We propose a triad of classic findings that should alert the clinician to check the patient's serum AAT levels, even in the absence of panniculitis on histologic evaluation. Consideration of this clinical triad may prevent delays in the diagnosis of AAT deficiency, as early lesions may not yet demonstrate subcutaneous fat involvement.