Topical Antibiotics Update

Nguyen HL, Yiannias JA. Contact Dermatitis to Medications and Skin Products. Clin Rev Allergy Immunol. 2019 Feb;56(1):41-59. doi: 10.1007/s12016-018-8705-0. PMID: 30145645.

Reviewed by Jalal Maghfour and Alina Goldenberg, MD, MAS

Topical medicaments contain a myriad of ingredients that have the potential to induce allergic contract dermatitis (ACD). While certain topical agents, particularly antibiotics have medical utility, there have been increasing reports on the adverse cutaneous reactions associated with their use.  In fact, the prevalence of ACD due to topical antibiotics (neomycin, bacitracin) is estimated to be between 7.2 to 11.8%.  Herein we provide an overview of ACD secondary to the use of topical antibiotics.

Neomycin, a member of aminoglycoside, is well known to cause mild to severe, localized cutaneous eruption in sensitized individuals. Topical neomycin has been shown to cross-react with other classes of antibiotics.   For instance, it has been reported that topical neomycin can cross-react with topical bacitracin, which can result in a synergic immune response.  While a localized cutaneous eruption is more common, use of topical bacitracin can result in an anaphylaxis reaction. Nowadays, this type of a systemic allergic reaction is rare and has been recently associated with irrigation of bacitracin in operating rooms.

Given the unique structure of mupirocin, individuals sensitized to bacitracin and aminoglycosides can use topical mupirocin as an alternative option.

However, mupirocin induced ACD has also been reported.  As with any ACD, symptoms vary and clinical manifestation ranges from localized erythema, stinging, pain, pruritus, and erythematous papular eruptions.

Patch testing remains the gold standard for diagnosis of ACD to topical antibiotics.  Nonetheless, for patients with allergic reaction to both topical neomycin and bacitracin, mupirocin remains an alternative therapeutic option.

Tea Tree Oil Update

de Groot AC, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016 Sep;75(3):129-43. doi: 10.1111/cod.12591. Epub 2016 May 13. PMID: 27173437.

Reviewed by Jalal Maghfour and Alina Goldenberg MD

Tee trea oil (TTO) is primarily derived from M. alternifolia, a tree plant native to Australia and can grow naturally in the northern coastal region of New South Wales.

TTO has been known to have a wide variety of health benefits and is considered to be an effective remedy for various skin disorders including acne, eczema and warts.

Although TTO has only been proven to be effective to treat small superficial wounds, it is increasingly being advertised and is a major ingredient in cosmetics and skin products.

As an essential oil, TTO is known to cause allergic contact reactions. In fact, of all essential oils, TTO makes up the majority of the literature on allergic reactions since 1991.

Herein, in this synopsis, we aim to provide a comprehensive overview of TTO, its uses, and composition.

TTO is a colourless to pale yellow, clear liquid extracted from the leaves with terminal branches of M. alternifolia.  Commercial TTO is primarily composed of terpinene family. Despite the recommendation set by the International Organization for Standardization (ISO) of essential oils, an analysis of 97 tee tree oil samples demonstrated the variability in the concentrations of the chemical components with some samples exceeding the recommended level.

Given the increase in reports of cutaneous reactions, TTO 5% has been added to the screening series of the North American Contact Dermatitis group (NACDG) since 2003; it is estimated that up to 3.5% of positive patch test reactions result from TTO sensitivity.  

Most of the positive patch test reactions are a result of direct sensitization to the following TTO components: ascaridole, terpinolene and α–terpinene.  Often time, the severity and extent of allergic reaction due to TTO depends on the type of products used. Application of pure oil can result in both local and systemic cutaneous reactions characterized by oozing and blistering.

It is important to note that the type of product use affects the shape and location of allergic reaction.  For instance, dermatitis in the eyelids/periorbital area can manifest following application of soap, cream and shampoo while the use of shaving oil can induce a cutaneous reaction in the involved area. Therefore, it is important for clinicians to inquire about all the products that may contain TTO.

Patch testing remains the diagnostic test of choice. It is recommended to use diluted TTO at 5-10% in pet vehicle.  At higher concentrations, severe allergic reactions may occur. Once the diagnosis is confirmed, it is important to counsel patients on the importance of avoiding products containing TTO.

Acrylics Update

Voller LM, Warshaw EM. Acrylates: new sources and new allergens. Clin Exp Dermatol. 2020;45(3):277-283. doi:10.1111/ced.14093

Reviewed by Jalal Maghfour and Alina Goldenberg MD

Acrylates, a group of synthetic thermoplastic resins, are becoming essential in industrial societies; they are commonly found in various nail products, adhesives, insulators, paints and windshields. Acrylates are known to cause allergic contact dermatitis (ACD) with the first documented case dating from 1941. ACD resulting from acrylates has been well-documented in the literature. In fact, acrylates were listed as the 2012 allergen of the year by the American Contact Dermatitis Society (ACDS).

Given the emergence of new sources of acrylates the aim of this synopsis is to highlight ACD associated with non-occupational and occupational acrylates exposure.

Non-occupational ACD secondary to acrylate exposure has been commonly reported. In 1995, Isobornyl acrylate (IBOA) was first documented to induce ACD during insulin infusion pump. Most recently, IBOA was isolated from the adhesives used primarily in many medical devices such as insulin pump and glucose monitors. This has resulted in IBOA becoming recognized as the 2020 allergen of the year by ACDS. Thus, diabetic patients and healthcare providers are particularly vulnerable to ACD due to IBOA.  

Acrylates contained in various artificial nail preparations are also a major source of sensitization. Cyanoacrylates are used in cosmetic and medical glues. There have been reports of ACD due to Dermabond which is a common surgical glue, due to its 2-octyl and cyanoacrylate ingredients.  

Occupational exposure to acrylates is also frequent.  Nail technicians are at high risk for developing acrylate allergy. Other fields such as orthodontists and dental technicians may be at increased risk for developing ACD given that the wide use of methacylates in dental prostheses.

As with any ACD, patch testing remains the gold standard diagnostic modality. Once an acrylate sensitization is diagnosed, patients should be adequately counseled on avoiding any cosmetic or industry products that contain acrylates. Workers at high-risk of exposure are recommended to wear trilaminated polyethylene gloves which  confer protection up to 4 hours. 

Cinnamon Synopsis

Ackermann L, Aalto-Korte K, Jolanki R, Alanko K. Occupational allergic contact dermatitis from cinnamon including one case from airborne exposure. Contact Dermatitis. 2009;60(2):96-99. doi:10.1111/j.1600-0536.2008.01486.x

Reviewed by Jalal Maghfour, Alina Goldenberg MD

Cinnamon is derived from the bark of cinnamon trees Cinnamomum Zeylanicum or Cinnamomum Cassia. Cinnamon has a versatile function and is widely used in food, pharmaceutical and cosmetic industries.

Allergic contact dermatitis (ACD) to cinnamon is very rare but has been reported by several authors across the literature. Cinnamal aldehyde is what makes cinnamon an allergenic compound. It also is what gives the rich odor and flavor to cinnamon. Upon contact with the skin, cinnamal aldehyde can act as an allergen. This binding results in an immune complex reaction that triggers the inflammatory cascade resulting in ACD.

Herein this synopsis we provide an overview of a study describing six patients who developed ACD due to a sensitization to cinnamon.

Of the six patients, three developed ACD primarily on the hands, where they had direct contact with cinnamon powder, contained in flour/rye. One patient developed ACD on the neck and face area presumably caused by airborne exposure to cinnamon in a working environment.

For diagnosis of any ACD, a detailed history and patch testing are required in order to identify the offending agent. However, spices are well known to be irritating in patch testing, which may result in high rate of false-positives.  Therefore, diluting series for patch testing is recommended for accurate diagnosis. Additionally, cinnamon is not commonly tested via patch testing, rather cinnamic aldehyde and cinnamal, strong sensitizers found in fragrances, are tested which can cross-react.   Therefore, patients with confirmed patch testing due to fragrance mix containing eugenol, cinnamal and cinnamyl alcohol should be counseled on the possible cross-reactivity with cinnamon. 

In summary, cinnamon is a very rare allergen, but has been reported to induce ACD. Patch testing is the gold standard diagnostic tool to elucidate an underlying cinnamon sensitivity.


PPD– Still a menace


Alina Goldenberg MD, Sharon Jacob MD. Paraphenylenediamine in black henna temporary tattoos: 12-year Food and Drug Administration data on incidence, symptoms, and outcomes. Journal of American Academy of Dermatology. April 201

https://www.jaad.org/article/S0190-9622(14)02217-8/abstract

Review by: Jalal Maghfour and Alina Goldenberg MD

Paraphenylenediamine (PPD) continues to be the main oxidizing agent widely utilized in the US for hair dyeing.  One of the major advantages of PPD, particularly in dark shades, is the resulting long-lasting color and the “natural” look that many individuals seek to achieve.

Given that PPD has been recognized as a strong sensitizing agent for several decades, it is solely approved for hair dye use with a concentration limited to 6%.

In the past decade, adverse reactions due to PPD have been on the rise; this has been seen primarily  when high amounts of PPD is mixed with black henna tattoos, which is a popular form of tattooing among travelers, as it is cheap and easy to remove. The addition of PPD to black henna offers a darker color that is appealing to costumers and enables a faster speeding dyeing process.

Yet, the physical and mental costs associated with local and systemic adverse effects of PPD are high and can be severely debilitating. Herein, the aim of this synopsis is to review the incidence, symptomatology and outcome among PPD-laced henna black tattoo users.

Even though PPD is limited to 6% in hair dye, it has been reported that black henna tattoo products may contain PPD concentrations of up to 30%. It is therefore not surprising that many individuals experience cutaneous reactions to PPD. In majority of cases, allergic contact dermatitis (ACD) including erythema, pruritus, and vesicular/bullous dermatitis may occur (67%). It is important to note that a primary sensitization to PPD is required for ACD to occur following a subsequent re-exposure. In addition, urticarial dermatitis was also reported as an adverse reaction (17%). The latter is a rare form of contact dermatitis that is mediated by an IgE induced mast cell degranulation resulting in hives and wheels. This type of dermatitis is highly concerning as it has been linked to anaphylactic shock.

It is also important to note that beyond localized reactions seen with PPD, systemic toxicity may also occur. Indeed, prolonged cutaneous exposure, at small or large doses for a long period of time, can result in systemic toxicity similar to the toxicity profile reported with PPD ingestion. A wide array of symptoms may be seen and can include the following: angioedema, acute hepatotoxicity, rhabdomyolysis, renal failure, neuropathy, blindness, and death.

Given the spike in severe cases of PPD laced black henna reactions reported by patients worldwide, Dermatitis, the official journal of the American Contact Dermatitis Society (ACDS), has listed PPD as the allergen of the year for 2006. In 2008, both ACDS and American Academy of Dermatology (AAD) officially opposed against the continuous use of PPD-laced black henna. This action has resulted in an increase in both physician and community member awareness as reflected by a lower number of reported cases following the joint ban from highly respected organizations.  

This commentary highlights not only the serious adverse effects of PPD but also puts into perspective the central role dermatologists and dermatology organizations can have in public awareness and education by advocating for patients’ safety.

What is essential in essential oil?

Reeder MJ. Allergic Contact Dermatitis to Fragrances. Dermatol Clin. 2020;38(3):371‐377. doi:10.1016/j.det.2020.02.009

Reviewed by Jalal Maghfour and Dr. Alina Goldenberg, MD

https://www.webmd.com/beauty/news/20180813/essential-oils-promise-help-but-beware-the-risks
https://www.poison.org/articles/2014-jun/essential-oils

Essential oils (EOs) are the quintessential oils in flowers, stems, seeds, leaves, roots and berries.  Although the name “essential” may imply purity, in reality, EOs are processed hydrophobic volatile compounds from raw plant material with various stabilizing additives.  Nevertheless, since ancient times, EOs have been used for skin beauty, cosmetics and treatments of various conditions such as pain and anxiety and continue to be highly marketed today despite their intrinsic risks.

The extraction of EOs is by no means simple. Common techniques for extraction include distillation and cold compression. Because of their hydrophobicity, the addition of a solvent is often required for both extraction and dilution of EOs. Solvents may include petroleum ether, methanol,  and ethanol  These solvents may be toxic pesticides such as methanol which has been associated with nausea, vomiting, headache, blurred vision, permanent blindness, seizures, coma, permanent damage to the nervous system or death. . Hence, there is no such a thing as “pure” essential oil.

Historically, EOs have been perceived as safe. This misconception is rooted from the fact that all herbs are considered safe because they are ‘natural’. This has led to an increase in use and misuse of EOs  With increased popularity of EOs for aromatherapy, there has been an expansion of EOs use in other products, even in EO products  advertised for their efficacy in treating various disorders including dermatologic conditions.  While the FDA can enforce guidelines to restrict how products are marketed, it is important to recognize that EOs are not FDA regulated.

It is therefore not surprising that increased accessibility of these products by the public has led to an increase in their use. In dermatology, EO induced Allergic contact dermatitis (ACD) is not new to clinicians but it is becoming increasingly more prevalent. In fact, fragrances, which also contain EOs as ingredients, have been designated as the 2007 allergen of the year, by the American Contact Dermatitis Society (ACDS).

EO-induced ACD is of clinical importance as standard patch testing may miss EO sensitizations. If there is high suspicion for an EO allergy, it is important to perform expanded patch testing to avoid false negative results. In the US, melaluca (tea tree) and ylang ylang are common allergenic oils that could be potentially missed if testing was limited to standard fragrance. 

Another common myth is that toxicity of EOs correlates with dose concentration. In reality, all EOs can be toxic at high concentrations but there are some types of EOs that are inherently toxic even at low doses, especially when taken orally . Camphor is a very toxic compound which can prove fatal for infants and children on ingestion even in very small doses. The strong aroma associated with camphor has attracted its use in many EOs, especially as a remedy for the common cold. Patients who ingested camphor can develop severe nausea, vomiting, lethargy, ataxia, and even seizures. Inhaling eucalyptus offers a soothing effect when suffering from a cold, however ingestion of eucalyptus oils can lead to seizures. Nutmeg is an EO which enhances food flavor; misusing it can lead to hallucinations and coma. Thus, even ‘safe’ EOs can be detrimental to patients if misused.  Even EOs advertised as non-toxic have the potential to be toxic to certain vulnerable individuals and age groups (babies, elderly) and/or if taken for a long period of time.  

In summary, although some EOs have been recognized to have beneficial properties, they have the potential to be extremely hazardous and dangerous to humans. It is vital for patients to appreciate the complexity of EOs and be aware of the fact that they are not as “pure” nor as free of risks as advertised.

The Empty Truths Behind “Hypoallergenic” Labeling

Zirwas MJ. Attempting to Define “Hypoallergenic”. JAMA Dermatol. 2017;153(11):1093‐1094. doi:10.1001/jamadermatol.2017.3045

Liem O, Kessen K, de Groot H. Hypoallergene dieren behoren tot het rijk der fabeldieren [Hypoallergenic animals, fact or myth?]. Ned Tijdschr Geneeskd. 2019;164:D4298. Published 2019 Dec 31.

Reviewed by Jalal Maghfour and Dr. Alina Goldenberg

Hypoallergenic is a term that has been traditionally associated with “allergens/fragrance free”.  Often time, products labeled as hypoallergenic are expensive and are advertised as a safe alternative for individuals who are sensitized to certain allergens.  Additionally, the term has gradually gained popularity in describing certain domestic animals, such as cats and dogs, that in theory, will not cause an allergic reaction. In reality, the term “hypoallergenic” is a dynamic word; its definition continues to evolve and change. 

In this synopsis, we focused on articles that discuss what the new criteria of hypoallergenic term is  and we hope, through this synopsis, to dismantle common misconceptions about hypoallergenic products as well as domesticated animals with the goal to aid clinicians in counseling patients suffering from allergic conditions.

The most important question to ask is: Are there any products that are truly hypoallergenic? The simple answer is “No”.  There are no such products that are “non-allergenic”. Instead, certain allergenic compounds can still be used if they induce a skin reaction at a low frequency in the general population.

Recently, the North American Contact Dermatitis Group (NACDG) has decided that for a product to be considered hypoallergenic it should not contain any allergenic ingredients that have a frequency of positive patch test results of 1 % or greater. This data was derived from a comprehensive patch test database containing at least 1,000 patients. While this frequency was set arbitrarily, it has been partially followed in practice—allergens yielding a positive patch test at a frequency greater than 1% are often added to screening trays used in patch testing.

In parallel, there is an increasing belief that some breeds/types of cats and dogs are hypoallergenic. This is a common misconception, as these types of animals do not exist. Instead, sensitized individuals may experience a reduction in skin reaction episodes in the presence of animals that shed less fur. This is because the offending allergen— dander (dead flaky skin), is often adherent to the fur which is shed at a different frequency based on the type of animal.

Hence, when counseling patients, it is important to emphasize that there are no such things as hypoallergenic products and/or animals. If manufacturers adhere to the 2017 NACDG definition of “hypoallergenic” for their product labeling, these products will truly be less likely to cause a skin reaction and will promote patients’ safety.

Unmask the facts- the truth behind “fragrance free”

Original Article:

Scheinman PL. Exposing covert fragrance chemicals. Am J Contact Dermat. 2001;12(4):225‐228. doi:10.1053/ajcd.2001.28697

Reviewed by Jalal Maghfour and Dr. Alina Goldenberg

Fragrances are widely used in personal care products, cosmetics, medicaments, and foods within the US. Fragrances are responsible for many cases of allergic contact dermatitis, leading it to be perceived as a significant public health problem. 

We aim to provide an overview of fragrance chemicals and how knowledge of fragrance elements can shape patient outcomes.

Patch testing continues to be the gold standard for the diagnosis of fragrance sensitization. Patch test commonly include fragrance mix (FM) and balsam of Peru. FM, which includes cinnamic aldehyde, cinnamic alcohol, eugenol, isoeugenol, hydroxycitronellal geraniol, oak moss absolute, and alpha-amyl cinnamic aldehyde,  is highly ubiquitous worldwide with an estimated sensitization prevalence of 11%.  

While patch testing can detect 70 to 80% of fragrance elements, false negative reactions to FM may occur. Hence, it is important to conduct an expanded series of fragrance chemicals if the suspicion for an allergy is high. This is of clinical importance since identification of the exact etiology may guide disease management and empowers patients to take control over their own health.

Although being aware of fragrance allergy is important, many products that are labeled as “fragrance-free” are not truly free of chemical fragrance. For instance, benzyl alcohol is often used as a preservative but it is also considered a fragrance agent. However, because benzyl alcohol has a dual function, companies can legally label a product as “fragrance-free”. This makes it challenging for sensitized patients to avoid certain “fragrance-free” products.  Hence, knowledge of various products by clinicians can be vital for patient care. Historically, plant and animal ingredients were the main extracts used in making fragrance. It is therefore important to note that a patient who is allergic to a fragrance agent in a product may also react to the same ingredient found in plants and flowers.  

Sensitization to an allergen is necessary for elicitation to occur in which the rash of ACD is present. Initial sensitization usually requires a higher dose of the chemical allergen. However, if a fragrance is applied to skin areas with high absorption capacity such as face, genitals, and traumatized areas (shaving, post-surgical sites, excoriated lesions of atopic dermatitis/eczema), a lower dose is may be necessary to sensitize an individual. It is noteworthy that for sensitized individuals subsequent exposure of a lower dose of the allergen may be enough to elicit a cutaneous eruption. Hence, in addition to removing fragrances from commonly used products, public policy should also focus on reducing the levels of fragrance use to prevent reactions in sensitized individuals.

Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention

Review and Synopsis by Jalal Maghfour, MD and Alina Goldenberg, MD of Original Peer-Reviewed Article:

Silverberg NB, Pelletier JL, Jacob SE, Schneider LC; SECTION ON DERMATOLOGY, SECTION ON ALLERGY AND IMMUNOLOGY. Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention. Pediatrics. 2020;145(5):e20200628. doi:10.1542/peds.2020-0628

Nickel (Ni) remains one of the most common causes of allergic contact dermatitis (ACD), a type IV hypersensitivity reaction, since the publication of its first case in 1888 by Dr. George Henry Fox. This metal continues to be highly prevalent in every day goods within the US. Ni ACD is considered a public health issue and has been gaining international attention.

The impact of nickel on both adults and children has been increasingly reported in the literature. However, Ni ACD is primarily a disease of the young as it rarely affects elderly (> 60 years). In this synopsis, we provide a brief overview on an article written by Silverberg et al. in which the authors discussed epidemiology, clinical presentation, pathogenesis and management of Ni ACD among pediatric population.

With the discovery of Ni in the 18th century and advancement in the steel industry in early 19th century, Ni has become commonly utilized among manufacturers and is now considered the 5th most common metal in the world. Ni ACD may manifest as mild pruritus with ill-defined erythema to diffuse and pronounced redness with oozing and bullae. Classically, Ni ACD presents as an erythematous lichenified papule/plaque and matches the object touching the specific skin area. Any parts of the body can be affected by nickel.

Ni ACD has a multifactorial etiology with a combination of genetic and environmental factors. Contact with nickel is simply not enough for a reaction to occur. The following conditions must be met for both induction and elicitation phase to occur: 1) Contact with a metal containing corroded Ni, 2) degree of solubility of Ni (higher the solubility the higher ion leakage); 3) Ni ions being absorbed by the skin.

In case of a Ni ACD, the majority of diagnoses are clinical. However, when the cutaneous patterns are atypical, the diagnosis may be difficult in which cases patch testing can be performed. Patch testing is the criterion standard method to diagnose Ni ACD. While it is usually a localized reaction, the appearance of 3 large papules following Ni patch testing strongly suggests a systemic nickel hypersensitization.  

Ni ACD can be a diagnostic challenge in AD patients as the morphologic eruption may not match the triggering object. In addition, patients may also experience an exacerbation of their AD. In parallel, adults with psoriasis often experience flare of their disease during a Ni ACD episode. Although Ni ACD is primarily a type IV reaction, immediate hypersensitivity through IgE has been reported as a cause of Ni ACD.

For Ni ACD treatment, this review recommends the avoidance of the offending agent as the next best step in management, followed by the treatment of inflammation with the use of glucocorticoids (potency is based on the affected area). Finally, restoration of the skin barrier is essential. This can be performed with a generous application of emollients. 

As exemplified by Denmark and Finland, enacting a national policy to regulate the amount of Ni that a population is exposed to was proven efficacious in reducing the rate of Ni ACD and has increased awareness on the topic among adolescents. There is no such regulation within the US. Because Ni is primarily found in jewelry and ear piercings, it may be beneficial to regulate Ni found in other forms of jewelry, as well as children’s toys, metal protectors for phone which are now increasingly recognized to as a cause of Ni ACD.

Increased production and manufacturing regulations, specific diagnoses and focused avoidance strategies can make Ni ACD a preventable pediatric health issue.  As it was shown with European countries, the United States can benefit from limiting Ni exposure to its population.  Until then, individual awareness and knowledge of daily objects containing nickel should be encouraged as part of avoidance.