Allergy Considerations in Implanted Neuromodulation Devices.

OBJECTIVES: Allergic reactions are rare and poorly understood complications of neuromodulation device implantation. There are currently no guidelines for management of allergic reactions to these devices and their components. Here we review the published cases of allergic reactions to implanted neuromodulatory devices and leverage the experiences of other specialties that deal with similar complications to formulate recommendations for prevention and management. MATERIALS AND METHODS: A review and assessment of the literature. RESULTS: Allergic reactions to a number of implantable devices have been observed and published. In dentistry and orthopedics, metals such as nickel are the most frequent cause of allergic reactions. In interventional cardiology, where devices closely resemble neuromodulatory devices, titanium, silicone, and polyurethanes are the most common causes of allergic reactions. In neurosurgery, allergic reactions to implantable neuromodulatory devices are rare, and we summarize 13 cases published to date. Such allergic reactions generally present as local dermatitis, erythema, and pruritus, which can be difficult to distinguish from surgical site infection. In one published case, symptoms resolved with corticosteroid treatment, but all other cases required explantation. The successful reimplantation with a modified device was reported in some cases. CONCLUSIONS: Patients should be screened for a personal history of contact allergy before implantation procedures. A multidisciplinary approach to suspected cases of postoperative allergic reactions involving collaboration between neurosurgeons and other implanting physicians, dermatologists or allergists, and device manufacturers is recommended. In cases where an allergic reaction is suspected, an infectious etiology should be ruled out first. Clinical suspicion can then be supported with the use of patch testing, interpreted by an experienced dermatologist or allergist. If patch testing supports an allergic etiology, the implanting physician and the device manufacturer can work together to modify the device for safe reimplantation.

Clinical factors before or after device implantation in predicting metal hypersensitivity reactions: A retrospective study.

BACKGROUND: Metal hypersensitivity reactions (MHR) as a cause of implant-related complications are highly debated and recommendations regarding pre-procedural allergy evaluation vary dramatically. OBJECTIVE: To examine patients referred before or after device implantation and identify factors that could be useful to guide the value of patch testing. METHODS: Patients who underwent patch testing pre- or post-device implantation between July 2006 and September 2016 were analyzed retrospectively. RESULTS: A series of 127 patients underwent patch testing: pre-implantation (n = 40) and post-implantation (n = 87). In the pre-implant group, a history of metal allergy demonstrated high sensitivity (0.94; 95% CI: 0.83-1.00) and negative likelihood ratio (0.17; 95% CI:0.02-1.29) for diagnosing MHR. No predictive value could be ascribed to any of the clinical symptoms (eg dermatitis, pain, swelling, implant failure, and/or other symptoms) for patients referred following orthopaedic and dental post device implantation. Eight patients in the orthopaedic group and six patients in dental group with relevant patch test reactions underwent implant revisions, and seven and five patients improved, respectively. CONCLUSIONS: Pre-implant patch testing for selected individuals with a history of metal allergy can help guide implant choice. Post-implant patch testing may be helpful in some patients if other causes have been excluded, as patients with confirmed MHR benefited from revisions.

Assessing the validity of self-reported history of rash caused by metal or jewellery.

BACKGROUND: The use of metal-containing bio-devices is becoming increasingly common. Self-reported history of dermatitis with metal exposure is not established as being predictive for metal allergy. OBJECTIVES: To assess the validity of two screening questions addressing metal allergy. METHODS: At Massachusetts General Hospital Contact Dermatitis Clinic, 2132 consecutive patients were asked either 'Do you get rashes when jewellery touches your skin' (Q1; N = 1816) or 'Do you get rashes when metal touches your skin?' (Q2; N = 316) before being patch tested. RESULTS: Testing showed that 20% of subjects had positive reactions to nickel, 7.4% had positive reactions to cobalt, and 5.8% had positive reactions to chromium. Q1 was 40% sensitive (95%CI: 35-45%). The positive predictive value (PPV) was 51%, and the negative predictive value (NPV) was 82%. Q2 was 77% sensitive (95%CI: 68-84%). The PPV was 71%, and the NPV was 84%. Q2 was 37% more sensitive than Q1 (p < 0.0001), with a higher relative risk (RR) (4.75, p < 0.001) than Q1 (RR = 3.01, p < 0.001). CONCLUSIONS: Patient-reported metal allergy, although not perfect, is a reasonable method for metal allergy screening to help identify those needing further objective evaluation by patch testing.

Successful Use of Cyclosporin A for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Three Children.

BACKGROUND/OBJECTIVES: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are medical emergencies. Mainstays of treatment include removal of the offending agent, supportive care, and wound care. The use of immunosuppressive agents such as corticosteroids and intravenous immunoglobulin (IVIg) is controversial. Some case reports and small studies report the successful use of cyclosporin A (CsA) for SJS/TEN in halting disease progression, fostering reepithelialization, and reducing mortality. OBJECTIVE: To report on the efficacy of cyclosporine A in the treatment of SJS/TEN in three pediatric patients. METHODS: We describe three pediatric patients seen at a tertiary care hospital in Boston, Massachusetts, diagnosed with SJS/TEN confirmed by skin biopsy who were successfully treated with CsA with improvements seen in time to cessation of disease progression or new lesion formation, reepithelialization, and duration of hospital stay. RESULTS: The average time cessation of disease progression or new lesion formation after CsA administration was 2.2 days (range 1.5-3 days) and average time to remission or reepithelialization was 13 days (range 10-15 days). The average length of hospital stay was 11.7 days (range 4-19 days). CONCLUSIONS: We describe three pediatric patients treated successfully with CsA and provide evidence for the use of cyclosporine in children with SJS/TEN. These results further support previous observations that CsA use for SJS/TEN produces consistently favorable outcomes. The results in this case series are limited by their observational nature. Additional trials are needed to evaluate the safety and efficacy of CsA use in children.

The brain circuitry mediating antipruritic effects of acupuncture.

Itch is an aversive sensory experience and while systemic therapies, such as acupuncture, have shown promise in alleviating itch in patients suffering from chronic itch, their antipruritic mechanisms are unknown. As several lines of evidence implicate brain-focused mechanisms, we applied functional magnetic resonance imaging and our validated temperature-modulation itch model to evaluate the underlying brain circuitry supporting allergen-induced itch reduction in atopic dermatitis patients by acupuncture, antihistamine, and respective placebo treatments. Brain response to allergen itch demonstrated phase dependency. During an increasing itch phase, activation was localized in anterior insula and striatum, regions associated with salience/interoception and motivation processing. Once itch reached peak plateau, robust activation was noted in prefrontal cognitive and premotor areas. Acupuncture reduced itch and itch-evoked activation in the insula, putamen, and premotor and prefrontal cortical areas. Neither itch sensation nor itch-evoked brain response was altered following antihistamine or placebo acupuncture. Greater itch reduction following acupuncture was associated with greater reduction in putamen response, a region implicated in motivation and habitual behavior underlying the urge to scratch, specifically implicating this region in acupuncture's antipruritic effects. Understanding brain circuitry underlying itch reduction following acupuncture and related neuromodulatory therapies will significantly impact the development and applicability of novel therapies to reduce an itch.

Hypersensitivity reactions to metallic implants - diagnostic algorithm and suggested patch test series for clinical use.

Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological devices are considered. Basic management suggestions are provided. Our goal is to provide a comprehensive reference for use by those evaluating suspected cutaneous and systemic metal hypersensitivity reactions.

A Novel Device that Reduces Preparation Times and Precision Mass Error in Patch Testing for Allergic Contact Dermatitis.

BACKGROUND: Patch test preparation for evaluation of allergic contact dermatitis is traditionally a slow process with inherent errors. OBJECTIVE: A novel device, referred to as a syringer, designed to dispense 10 unique petroleum-based haptens simultaneously, significantly reduces preparation time and increases the precision of the mass dispensed per well. METHODS: The syringer was custom designed and "printed" through the use of a 3-dimensional printer with a polylactic acid plastic medium. RESULTS: The syringer dispensed 10 haptens significantly (P < 0.05) faster: 6.9 seconds on average, compared with 29.6 seconds by the traditional method. The syringer demonstrated a significantly (P < 0.05) lower average deviation of each strip's per-well mass average compared with the traditional method. CONCLUSIONS: In practice, this syringer is ideal for preparing patient-ready patch tests in quantities of 2 identical strips or more.

Patch Testing Results From the Massachusetts General Hospital Contact Dermatitis Clinic, 2007-2016.

BACKGROUND: Patch testing is the criterion standard for diagnosis of allergic contact dermatitis (ACD). OBJECTIVE: The aim of the study was to report the trends of patch testing results with the standard series at Massachusetts General Hospital from January 1, 2007, to December 31, 2016, compared with previous data from 1998 to 2006 and from 1990 to 2006 and those reported by the North American Contact Dermatitis Group. METHODS: Data were collected and analyzed from retrospective chart reviews, focusing on 50 allergens in our standard series. RESULTS: A total of 2373 patients were patch tested. One or more positive reactions were observed in 1428 patients (60.2%), and 1153 patients (48.6%) had a final primary diagnosis of ACD. Top 5 allergens were nickel (19.8%), fragrance mix I (14.6%), Myroxylon pereirae (balsam of Peru) (13.5%), neomycin (9.4%), and bacitracin (7.7%). Sensitization frequencies statistically increased over time for 3 allergens: nickel, neomycin, and propylene glycol, and decreased for 5 allergens: formaldehyde, paraben mix, thiuram mix, n-isopropyl-N-phenyl-4-phenylenediamine, and epoxy resin (P ≤ 0.001). CONCLUSIONS: Surveillance of ACD trends is essential to detect emerging sensitizers. Patch testing is an important diagnostic tool for detection of ACD to commonly encountered and potential allergens.

Patch Testing With an Extended Metal Allergen Series at the Massachusetts General Hospital (2006-2017).

BACKGROUND: Reports of patch test data with an extended metal series that includes rare metals are limited. OBJECTIVE: The aims of the study were to analyze and report patch testing results from an extended metal series, examine associations with sex and age, and highlight concomitant metal reactions. METHODS: This study is a retrospective review of 150 patients referred for suspected metal allergy from January 1, 2007, to December 31, 2016. RESULTS: The most common indications for evaluation referral were those having symptoms after implantation of a metal device (55.3%) and those with a history and concern of metal allergy before implantation of a metal device (22.0%). One or more positive patch test reactions were observed in 87 patients (58.0%). Metals with the highest frequencies were nickel sulfate 2.5% (26.2%), gold sodium thiosulfate 0.5% (23.0%), gold sodium thiosulfate 2.0% (20.7%), palladium chloride 2.0% (19.6%), cobalt chloride 1.0% (12.0%), and manganese chloride 2.0% (10.1%). Of the 45 metals tested, 15 caused no patch test reactions. Female patients were more likely to be sensitized to nickel, gold, and palladium (P < 0.05). Younger patients (≤40 years) had higher reaction rates to nickel, mercury, palladium, and cobalt. Concomitant reactions of the top metals (nickel, palladium, gold, and cobalt) were statistically associated bidirectionally (P < 0.05), except for cobalt and gold. CONCLUSIONS: Allergy to metals, including those not included in standard series, may be more prevalent than previously suspected. Results may help guide future testing for suspected metal allergy, although future studies are warranted.

American Contact Dermatitis Society Core Allergen Series: 2020 Update.

The American Contact Dermatitis Society Core Allergen series was introduced in 2013 and updated in 2017. Changes in our recommended allergens are again necessary, taking into account data from the American Contact Dermatitis Society's Contact Allergen Management Program top 100 allergens from 2018. For the updated series, we removed methyldibromoglutaronitrile and added new haptens: Lyral, Limonene, Linalool, carmine, benzyl salicylate, disperse yellow 3, jasmine, peppermint, pramoxine, shellac, and lauryl polyglucose (glucosides). These additional allergens should increase the yield of relevant positive reactions for our patients.

Rashes and other hypersensitivity reactions associated with antiepileptic drugs: A review of current literature.

This article provides an overview of the pathogenesis and risk factors associated with antiepileptic drug (AED) hypersensitivity reactions, provides prescribing guidelines that may minimize the risk of antiepileptic induced rashes, and discusses treatment options for rashes. Articles indexed in PubMed, Science Citation, and Google Scholar (January 1946-March 2019) were systematic searched using the following key terms: hypersensitivity, rash, antiepileptic, epilepsy, cross-sensitivity, desensitization, patch testing and supplemented with our clinical experiences. Additional references were identified from a review of literature citations. AEDs are associated with cutaneous adverse reactions. Aromatic AEDs and higher titration rates are associated with increased risk of hypersensitivity reaction. Patient characteristics, underlying health conditions, and genetic variations may increase the likelihood of a hypersensitivity reaction. Once a hypersensitivity reaction occurs, the likelihood of cross sensitivity to another AED increases, especially among other aromatic AEDs. Withdrawal of the causal agent and initiation of a lower risk agent usually leads to resolution of symptoms. Desensitization protocols may be an option for patients whose seizures only respond to the AED causing the rash.

The Medical Necessity of Comprehensive Patch Testing.

Allergic contact dermatitis is associated with significant disease and economic burden in the United States. To properly manage allergic contact dermatitis, it is important to accurately identify the substance(s) implicated in the dermatitis to prevent disease recurrence. The commercially available T.R.U.E Test (36 allergens) screening panel has been reported to have a conservative hypothetical allergen detection rate of 66.0%, at most. Importantly, these calculations are based on the 78% of patients who had clinically relevant reactions to allergens present on the North American Contact Dermatitis Group screening series (70 allergens), without the use of supplemental allergens. Testing with supplemental allergens beyond a screening series can more fully evaluate an individual's environmental and occupational exposure, which may significantly increase diagnostic accuracy. Comprehensive patch testing with additional allergens in sunscreens, cosmetics, and fragrances, for example, may increase the diagnostic yield as well as the likelihood of achieving a cure if the dermatitis is chronic and recalcitrant.

Survey of Patch Test Business Models in the United States by the American Contact Dermatitis Society.

BACKGROUND: Allergic contact dermatitis (ACD) remains a significant burden of disease in the United States. Patch testing is the criterion standard for diagnosing ACD, but its use may be limited by reimbursement challenges. OBJECTIVE: This study aimed to assess the current rate of patch test utilization among dermatologists in academic, group, or private practice settings to understand different patch testing business models that address these reimbursement challenges. METHODS: All members of the American Contact Dermatitis Society received an online survey regarding their experiences with patch testing and reimbursement. RESULTS: A "yes" response was received from 28% of survey participants to the question, "Are you or have you been less inclined to administer patch tests or see patients needing patch tests due to challenges with receiving compensation for patch testing?" The most commonly reported barriers include inadequate insurance reimbursement and lack of departmental support. CONCLUSIONS: Compensation challenges to patch testing limit patient access to appropriate diagnosis and management of ACD. This can be addressed through a variety of innovative business models, including raising patch testing caps, negotiating relative value unit compensation, using a fixed salary model with directorship support from the hospital, and raising the percentages of collection reimbursement for physicians.

Acneiform reaction to erlotinib.

Erlotinib is a reversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) newly approved for the treatment of refractory, locally advanced, or metastatic nonsmall cell lung cancer. Acneiform skin reactions with EGFR inhibitors are common, with a dose-dependent skin reaction being seen in 50 to 100% of patients. This case illustrates the typical skin reaction seen with EGFR-TK inhibitors and illustrates the lack of reaction in skin with sebaceous glands that have been destroyed by radiation. Discussion of this skin reaction in the literature of dermatology is limited; this case illustrates a pattern of reaction that may suggest a mechanism for this skin reaction pattern to erlotinib.

Metal Hypersensitivity Reactions to Orthopedic Implants.

Total hip and knee replacement surgery using metal alloy devices is common. Type IV allergic reactions to these implants occur, though infrequently. While uncommon, peri-implant metal allergic reactions may cause significant morbidity for the affected individual-including aseptic loosening, pseudotumor formation and frank device failure. It is challenging to predict who will have these reactions, even in those with established pre-implant metal allergy. At this time, the scientific literature clearly supports few conclusions. Despite this, we believe several conclusions can be made: routine pre-implant testing in asymptomatic individuals is not indicated; listen to patient's concerns about metal allergy if the concern arises; patch testing is probably the best pre- and post-implant screening test; post-implantation testing is controversial and even positive LTT or patch test does not definitively diagnose morbidity from a metal allergy; and complete recovery following revision placement of an immunologically inert device is diagnostic. More research is needed to scientifically approach this issue.

American Contact Dermatitis Society Core Allergen Series: 2017 Update.

The American Contact Dermatitis Society Core Allergen Series was introduced in 2012. After 4 years of use, changes in our recommended allergens are necessary. For the updated series, we have reordered the first 4 panels to approximately mirror the current TRUE Test and removed parthenolide, triclosan, glutaraldehyde, and jasmine. Polymyxin B, lavender, sodium benzoate, ethylhexylglycerin, and benzoic acid are new additions to the American Contact Dermatitis Society series.