Douglas L. Powell

Contact urticaria from curcumin.

&NA; Turmeric, a spice derived from the rhizome of the plant Curcuma longa, contains the chemical curcumin, which is responsible for turmerics taste, color, and biologic properties. Curcumin is used as a spice in foods, as a treatment in traditional medicine, as a dye for fur, and as a component in nutritional supplements. A few cases of allergic contact dermatitis from curcumin have been reported. We report two cases of contact urticaria from curcumin. These cases are mediated by two different mechanisms of contact urticaria: nonimmunologic and immunologic (immunoglobulin‐E mediated).

Facial Allergic Granulomatous Reaction and Systemic Hypersensitivity Associated With Microneedle Therapy for Skin Rejuvenation

IMPORTANCE Microneedle therapy includes skin puncture with multiple micro-sized needles to promote skin rejuvenation or increase transdermal delivery of topical medications. In cosmetic practices, various cosmeceuticals are applied before microneedling to enhance the therapeutic effects. This results in intradermal tattooing of the topical product. Despite rapid increase in the use of microneedles in dermatology, there are few data about their safety. OBSERVATIONS We describe 3 women, aged 40s to 60s, who developed open [corrected] facial granulomas following microneedle therapy for skin rejuvenation. Two patients had undergone microinjection of the same branded topical moisturizer (Vita C Serum; Sanítas Skincare) during microneedle therapy. Biopsy in all cases showed foreign body-type granulomas. Results of tissue cultures were negative. Chest radiography and serum angiotensin-converting enzyme findings were normal. The first 2 patients had a positive patch test reaction to Vita C Serum. Initial treatment with topical and oral corticosteroids was ineffective. Therapy with doxycycline hydrochloride and minocycline hydrochloride led to partial improvement in one case and resolution in another. CONCLUSIONS AND RELEVANCE Application of topical products prior to microneedling can introduce immunogenic particles into the dermis and potentiate local or systemic hypersensitivity reactions. Because the microneedle therapy system is accessible for home use, health care providers need to be aware of its potential consequences.

Unusual presentation of nickel allergy requiring explantation of an Amplatzer atrial septal occluder device.

Systemic allergic reaction to a percutaneous patent foramen ovale (PFO) occlusion device is a rare event with only scattered reports in the literature. Serious allergic reactions to these devices have a poorly defined incidence, presentation, and natural history. We present a woman with a previously unknown nickel allergy who developed severe chest pain beginning the morning after percutaneous device closure of the PFO. Despite multiple visits to her cardiologists and primary care physicians, the cause of her chest pain remained unclear. After seeking a second opinion at our medical center, skin testing showed a severe reaction to nickel. These symptoms were refractory to treatment until device explantation 18 mo later. This case highlights the importance of recognizing nickel allergy as a cause of chest pain following implantation of certain types of devices used for closure of PFOs and other heart defects. Copyright

Treatment of refractory chronic urticaria with tumor necrosis factor–alfa inhibitors

To the Editor: Chronic urticaria is a physically and emotionally debilitating condition that often fails to respond adequately to antihistamines. Systemic therapy with glucocorticoids, sulfasalazine, colchicine, intravenous immunoglobulin, dapsone, or other immunosuppressants including cyclosporine, cyclophosphamide, and methotrexate are used in many patients with the associated risks of renal and hepatic toxicity and anemia. Unfortunately, some patients have disease recalcitrant to these treatments. The pathogenic mechanisms of chronic urticaria are not well understood, but the primary effector cell is likely the mast cell. Activated mast cells release mediators, including tumor necrosis factorealfa (TNF-a), that recruit other immune cells and play a role in perpetuating an urticarial response. TNF-a is known to exist preformed in mast cells and to be newly synthesized upon mast cell activation. Several preclinical investigations have shown an upregulation of TNF-a in patients with chronic urticaria. Magerl et al described a patient with severe psoriasis and delayed pressure urticaria who became free of urticarial lesions after 4 days of treatment with etanercept. Based on these preclinical investigations and the case report, we treated six of our most refractory chronic urticaria patients with TNF-a inhibitors. The choice of TNF-awas primarily based on the patient’s insurance and our experience using the medications. When possible, we used doses tested for other systemic inflammatory conditions, such as psoriasis. A brief summary of each patient’s background and treatment course is provided in Table I. The theoretical basis for the use of TNF-ae targeting therapy to treat urticaria is supported by studies that have shown the upregulation of TNF-a in chronic urticaria. In a study of 19 chronic urticaria patients and 15 healthy controls, cytokine and chemokine production after autologous serum skin testing was analyzed and TNF-a, interleukin (IL)-10, RANTES, and macrophage inflammatory protein1a were upregulated in chronic urticaria patients but not controls. In another study that compared levels of TNF-a in lesional and nonlesional skin of chronic urticaria patients, TNF-a was found to be expressed throughout the epidermis in lesional and nonlesional chronic urticaria skin but not in control skin. Furthermore, a study by Piconi et al revealed similar immunologic profiles in patients with chronic urticaria and with rheumatoid arthritis, psoriasis, and psoriatic arthritis, with increased expression of TNF-a and IL-10, and decreased expression of IL-2 and interferon gamma. Interestingly, these diseases, along with chronic urticaria, tend to worsen with infection. Perhaps a common linkmay be an aberrant response of innate immunity mediated through TNF-a expression. In our series of six patients who were recalcitrant to all other immunosuppressive therapies, we observed dramatic improvement with TNF-a inhibitors. In most cases, the improvement was durable, lasting for several years, and in three cases the patients were subsequently tapered off all systemic treatment and their urticaria remains in remission. These results suggest that targeted TNF-a therapy may be useful for disease refractory to conventional or immunosuppressive therapy. Larger, controlled studies with longer followeup periods are needed to further confirm the efficacy and safety of TNF-a inhibitors in the management of patients with chronic urticaria.

Interatrial shunt closure devices in patients with nickel allergy

We assessed outcomes in nickel allergic patients treated with percutaneous interatrial shunt device closure with the Helex device. Nickel toxicity has been well described in patients undergoing interatrial shunt closure with the Amplatzer device, which has a nitinol design. There have been no reports using Helex in nickel allergic patients. Ninety‐five consecutive patients underwent percutaneous interatrial shunt closure at a single US center by one operator. In those with possible nickel allergy, patch testing with the North American Contact Dermatitis Group standard series and a metal series was performed. The mean age was 48 ± 16 years (range 18‐81), 48% were male, 21 (22%) had atrial septal defect, and 74 (78%) had patent foramen ovale. Six patients had a positive skin test to nickel and underwent successful closure with Helex. Of the remaining 89 patients, 88 were closed with Amplatzer and one with Helex. All procedures were successful with no deaths, myocardial infarctions, strokes, or systemic emboli at six‐month followup. None of the Helex patients developed an allergic reaction, significant chest pain, or arrhythmia. Of those without pre‐procedural known nickel allergy, 12% had palpitations, 5% had atrial fibrillation, and 13% had chest pain. When compared with a published report that 89% of nickel‐allergic patients developing an allergic reaction to the Amplatzer or Premere device, Helex appeared far safer in nickel allergic patients (P < 0.001). In patients with nickel allergy, percutaneous interatrial shunt device closure with Helex device is safe, and is not associated with allergy to nickel.

Pediatric Contact Dermatitis Registry Inaugural Case Data

BackgroundLittle is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. ObjectiveThe aim was to quantify patch test results from providers evaluating US children. MethodsThe 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). ResultsOne 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%). ConclusionsThis 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.

Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society.

The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion–based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantation morbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient.

Contact Urticaria to Nickel: A Series of 11 Patients Who Were Prick Test Positive and Patch Test Negative to Nickel Sulfate 2.5% and 5.0%

BackgroundNickel is the most common allergen found by patch testing; however, not all cases of nickel allergy are type 4 (delayed) allergies. Contact urticaria (CU) to nickel (immediate reaction) has been reported; however, few seem to evaluate it as per a recent published survey of American Contact Dermatitis Society members. ObjectiveThe aim of the study was to present a series of patients who had clinical histories suggestive of nickel allergy and yet were patch test negative but prick test positive to nickel, thus demonstrating CU. MethodsWe reviewed the charts of 11 patients who were patch test negative but prick test positive. ResultsAll 11 patients demonstrated evidence of CU by prick testing (or closed chamber test in 1). None were patch test positive to nickel 2.5% or 5.0%. Four patients’ histories mentioned reactions to various jewelry/earrings within minutes, whereas 2 histories mentioned reacting within a few hours. These histories are consistent with CU. Others (except 1 patient) recalled reacting to jewelry/earrings but did not recall a time frame. ConclusionsOur series suggests that CU to nickel may be far more common than anticipated and should be evaluated with prick testing when patients’ history suggests nickel allergy and yet they are patch test negative.

Prevalence and interest in the practice of scratch testing for contact urticaria: a survey of the American contact dermatitis society members.

BackgroundContact urticaria (CU) is the development of a wheal and flare on the skin after topical exposure to a particular chemical or compound. It can be diagnosed through a variety of techniques. Many chemicals that cause a type IV allergy can also cause CU. The incidence of CU to these chemicals is unknown. ObjectiveThe aim of this study was to evaluate the opinions of the American Contact Dermatitis Society members regarding CU and scratch testing. MethodsWe distributed an electronic survey to the American Contact Dermatitis Society members regarding observed prevalence of CU, frequency of scratch testing in clinical practice, and interest in learning about scratch testing in diagnosing CU and other skin contact conditions. ResultsWe distributed 508 surveys and received 133 responses. Seventeen percent reported that CU was extremely rare, 32% reported that CU was rare, and 38.9% reported that CU was infrequent. Alternatively, 10.7% believed that CU was common, and 1.5% believed that CU was extremely common. A minority, 19.1%, performed scratch testing on patients with suspected CU. Most respondents, 54.6%, were interested in learning about scratch testing. ConclusionsAdditional education regarding scratch testing could increase comfort and use of scratch testing in clinical practice. Further studies are needed to evaluate the prevalence of CU in the general population and better guide the use of testing for dermatologic patients.

Contact Urticaria From Occupational Exposure to Formaldehyde.

To the Editor: Formaldehyde, known to cause allergic contact dermatitis in sensitized individuals, is rarely reported to cause contact urticaria (CU). We present 2 cases of CU from occupational exposure to formaldehyde. First is a 26-year-old otherwise healthy woman, employed 3 years as a histology technician in a dermatopathology laboratory, who presented with a 1-month history of sneezing and an itchy rash on her arms, legs, and nose occurring only within 30 minutes of working under a ventilation hood processing formalin-fixed specimens. Symptoms resolved 15 minutes after moving away from the hood. Physical examination was unremarkable. Patch testing was performed using the American Contact Dermatitis Society core series, and readings were done at 48 and 96 hours. Results revealed an irritant-type reaction to propolis but was no reaction to all others, including formaldehyde. Skin prick testing was performed using formaldehyde 1% AQ and the 7 formaldehyde releasers from the American Contact Dermatitis Society core series. Formaldehyde 1% caused an itchy 6-mm wheal with flare extending 15 mm at 15 minutes. All formaldehyde releasers were negative by prick testing. Positive and negative controls were also performed on this patient. Second is a 45-year-old female dermatologist with a history of asthma flares when exposed to formalin (40% formaldehyde) in the grossing room. Patch testing was not performed. Prick testing was performed as above with 1% formaldehyde. Immediately, she experienced a large 1-cm wheal, generalized pruritus, paleness, and a severe asthma flare. She dramatically improved with intramuscular Benadryl, but her asthma recurred within 10 minutes. The patient became light-headed and hypotensive and was given intramuscular epinephrine. Her asthma subsided and hypotension resolved. She was prescribed an epinephrine pen because her work required periodic exposure to formalin. Seven control patients were negative to prick testing with 1% formaldehyde. Formaldehyde, a common preservative and the 2015 Contact Allergen of the Year, most typically causes allergic contact dermatitis. Formaldehyde vapors can be an irritant to mucous membranes, especially for atopic persons with an impaired skin barrier. Reports of CU from formaldehyde are rare, with occupational CU cases reported in a leather-handler, surgical nurse, and pathology laboratory worker. Of note, the laboratory worker’s CU was believed to be caused by formaldehyde vapors. Contact urticaria reactions are divided into 3 categories based on etiology: nonimmunologic/irritant, immunologic/ allergic, and mixed (idiopathic). Nonimmunologic CU occurs without prior sensitization, with causative agents theoretically able to trigger an urticarial reaction in anyone who comes into contact with them. Examples include stinging nettles, benzoic acid, and cinnamaldehyde. Immunologic CU (ICU) is a rarer type I hypersensitivity reaction resulting from previous sensitization to the offending agent. In addition to the classic wheal-and-flare cutaneous manifestation, ICU can also involve rhinitis, conjunctivitis, asthma, or even shock. Because of the systemic symptoms in both our patients, we believe that both represent ICU. Contact urticaria should be considered when evaluating patients with a history of respiratory distress when exposed to formaldehyde vapors. The combination of these 2 patient cases may suggest a possible increased risk of ICU in persons working in a dermatopathology laboratory.