NatalieLaser-Induced Edgar, DO,* Molly Buckland, Urticaria: DO,** Richard A. Miller, A DO***Case Report and Review of Physical Urticaria

*Dermatology Resident, Nova Southeastern University College of Osteopathic Medicine/Largo Medical Center, Largo, FL **Traditional Rotating Intern, Nova Southeastern University College of Osteopathic Medicine/Largo Medical Center, Largo, FL ***Program Director, Dermatology Residency, Nova Southeastern University College of Osteopathic Medicine/Largo Medical Center, Largo, FL

Disclosures: None Correspondence: Molly Buckland, DO; [email protected]

Abstract Mild urtication following laser hair removal treatment is a normal finding, but severe urticarial reactions are rare. Laser-induced urticaria is caused by an external stimulus and is reproducible with subsequent exposures, suggesting that it is a type of physical urticaria. Herein, we highlight a case of a 46-year-old female who developed a severe urticarial reaction following laser hair removal treatment. We also explore potential causes and offer a review of physical urticaria subtypes.

Introduction but without the topical skin protectant. Following Chronic urticaria is a debilitating disease that this treatment, the patient had a similar reaction greatly impacts a patient’s quality of life. Often, that included initial follicular urticarial papules disease etiologies and triggers can be almost that worsened over hours into diffuse urticaria impossible to determine. In physical urticarias, of the lower extremities (Figures 1-3). Oral which are clinical subtypes of chronic urticaria, diphenhydramine 50 mg every six hours helped to an external stimulus induces a wheal-and-flare alleviate some of the associated pruritus. Again, reaction and/or angioedema.1 Responsible for the urticarial eruption lasted for about 72 hours. up to 25% of chronic urticaria cases, physical Our patient decided to undergo a third laser hair urticarias are divided into distinct subtypes that removal treatment several weeks later, which are categorized based on whether the stimulus is resulted in an identical outcome. mechanical, thermal, or electromagnetic.1 Exactly These recurrent and reproducible reactions how these stimuli trigger urticarial lesions is prompted the consideration of laser-induced unclear, but it is postulated that it may result from 1,2 urticaria or another underlying physical urticaria in a heightened sensitivity of mast cells. this patient. The patient denied having a history of While it is not uncommon for urticarial papules to regular urticaria but did report one urticarial event develop around each treated follicle after laser hair four years prior, which was attributed to a shampoo removal, it is usually transient and not clinically sensitivity that resulted in swelling and pruritus of significant.3 Here, we report a case of severe her scalp and eyelids. Figure 1. Wheal-and-flare reaction of the left lower urticaria that developed in a patient following On exam, the patient did not exhibit laser hair removal treatment and explore possible leg 24 hours following laser hair removal treatment. dermatographism. She also specifically denied any etiologies for the occurrence. history of an urticarial or other pruritic eruption Case Report following exposure to cold, heat, sunlight, pressure, A 46-year-old female was treated in the office with a emotional stress, exercise, spicy foods, or previous newly acquired diode 810-nm laser (large sapphire laser treatments. She denied history of any optic Vectus® hair removal laser, Cynosure). The ongoing medical problems and denied taking any patient requested treatment of her legs bilaterally medications. to remove unwanted hair, a procedure she had undergone in the past without complications. She Discussion Laser hair removal has become a popular and had Fitzpatrick skin type II. Based on her skin effective cosmetic procedure for the long-term type and hair characteristics, laser settings of 38 J/ 2 reduction of terminal body hair. Long-pulse cm with a pulse duration of 10 ms and a spot size lasers emitting visible and infrared radiation of 23 mm x 38 mm were utilized for her treatment. target specific chromophores, such as melanin Throughout the procedure, an overlap of 50% was pigment, contained in the hair shafts, resulting in performed, and Lux Lotion® was utilized as a 3 thermal damage to the hair follicle. The resultant skin protectant. Upon treatment completion, the Figure 2. Urticarial eruption of the right lower leg inflammatory response triggers anagen follicles to patient began to complain of pruritus and redness 24 hours following laser hair removal treatment. shed terminal hair, which is then replaced by vellus of the treated areas. The pruritus worsened over 3 hair. Lasers often used for hair removal include time, and she began to develop a diffuse and those employing the red or infrared wavelengths, significant wheal-and-flare reaction. She denied such as the 755-nm alexandrite laser, the 810- oral and pharyngeal swelling as well as shortness nm diode laser, and the 1,064 neodymium-doped of breath. The urticaria improved 24 hours after 3 yttrium aluminum garnet (Nd:YAG) laser. the procedure, and by 72 hours post procedure the Epidermal surface cooling is utilized to protect the lesions had subsided. epidermis from heat injury if epidermal melanin Approximately six weeks following her initial is inadvertently targeted during laser treatment. treatment, the patient requested a second laser The most common adverse effect of laser hair removal treatment is skin hyperpigmentation hair removal treatment of the lower extremities. 3 The patient believed that her previous reaction or hypopigmentation. Additionally, transient, was likely secondary to the Lux Lotion® skin small, follicular urticarial papules commonly result protectant used during the initial treatment, as she immediately following most laser procedures; reported a history of sensitivity to an unknown however, significant urticaria or edema following laser hair removal is rare.4 The normal urticarial substance in some topical products, including Figure 3. Edematous papules and plaques with cosmetics. The patient was treated for a second response is usually confined to the immediate surrounding erythema on the lower extremity 24 time with the hair removal laser on the bilateral area surrounding the hair shaft but may be lower extremities using the same laser settings accompanied by a subtle urticarial response in the hours following laser hair removal treatment.

EDGAR, BUCKLAND, MILLER entire treatment area, which can last for anywhere methods. Our patient’s wheal-and-flare reaction last for 30 minutes to 2 hours.2 The diagnosis of from minutes to 24 hours.3 occurred only after each treatment (total of three) dermatographism is made by provocation testing, by with the Vectus laser. Landa et al. described using either a dermographometer or a blunt-tipped Cases of pathological urticaria following laser urticaria after treatment with 755-nm alexandrite object to stimulate the skin. The underlying causes treatment have been reported in the literature. lasers; however, the persistent urticaria could not of dermatographism have not been elucidated fully. Bernstein et al. described four cases of severe be reproduced with the cryogen spray alone.4 A It has been postulated that some medications (e.g., urticaria and edema following laser hair removal direct link between the cooling mechanism and progesterone, atorvastatin), various infections (e.g., that developed immediately and persisted for up persistent urticaria has not been shown. As in our respiratory, dental, hepatitis), or diabetes mellitus 3 to one week. Three of the patients were treated case, none of the reports involved patients with a might play a role in its pathogenesis.1 with a 755-nm alexandrite laser and one with the history of cold-induced urticaria, making cold- 1,064 Nd:YAG laser; both lasers utilized cryogen induced urticaria an unlikely cause. During laser hair removal treatment using the cooling. Like our patient, these patients had Vectus diode 810-nm laser, the laser head must tolerated previous laser treatments and had no Heat-induced urticaria be placed firmly on the skin. There is a possibility history of physical urticaria. Landa et al. studied Heat contact urticaria is a rare type of physical that the application of the device directly onto 36 patients who developed persistent urticaria urticaria, with fewer than 100 cases reported in the skin caused a dermatographism-like reaction following laser hair removal with the 755-nm the literature.1 Symptoms usually develop within in the patient presented in this case. She did alexandrite laser.4 The rash developed six hours to minutes of heat exposure to the skin and typically experience pruritus along with a wheal-and- 72 hours after treatment and resolved within seven resolve within a few hours. The skin lesions are flare reaction. However, her lesions lasted much days to 30 days. Most of the reactions occurred limited to the area exposed and are generally well longer than one would expect from symptomatic in the first treatment; however, 10 cases developed defined. The diagnosis is confirmed by local heat dermatographism. Additionally, our patient did not a reaction during the second, third, or fourth (45◦C) applied for five minutes.2 It is unlikely that exhibit dermatographism with provocation testing. treatment. In 31 of the 36 cases, the reaction heat-induced urticaria is the cause of the reaction occurred on the legs. It is important to note in our case, as the patient had never experienced Contact urticaria that a previous history of allergies was reported urticaria upon skin contact with hot objects in the Urticarial reactions may occur with certain skin by 33 out of 36 patients; however, none of the past. The timeline of our patient’s wheal-and-flare exposures. The pathogenesis behind this reaction patients studied had a history of physical urticaria. reaction also does not fit with the classic symptoms can be allergic or non-immunologic. Allergic Moreno-Arias et al. described a case of intensely of heat-induced urticaria, which usually resolve contact urticaria involves an IgE-mediated release 8 pruritic urticarial vasculitis after treatment with a within a few hours. of vasoactive compounds after a specific exposure. LightSheer® diode laser that developed 24 hours Alternatively, non-immunologic contact urticaria after the patient’s second treatment.3,5 Delayed pressure urticaria is not antibody mediated and occurs due to a This subtype of physical urticaria is defined by direct release of vasoactive substances.8 Often, Laser-induced urticaria is likely to be a physical the development of angioedema due to prolonged cosmetic products cause contact urticaria. In this urticaria due to its inducible and often reproducible pressure to the skin. This reaction is delayed in patient, the urticaria following laser hair removal nature; however, in some cases, it can be difficult onset and usually occurs six hours to eight hours was initially thought to be secondary to the Lux to categorize into an existing subtype of physical after the original stimulus, but can occur in as little Lotion used during the first session. Lux Lotion urticaria. The following discussion will explore as 30 minutes.2 Lesions may persist for up to 72 contains propylene glycol, water, fructose, liquid potential causes of our patient’s urticaria, including hours. Unlike the other physical urticarias, delayed glucose (corn syrup), sucrose, and L-glutamic acid. a review of physical urticaria subtypes that might pressure urticaria may be associated with burning Propylene glycol has been implicated as a common have played a role in our case. These physical pain and even systemic symptoms, making it a contact allergen, especially in cosmetic products, urticarias include solar urticaria, cholinergic potentially debilitating disease. There are reports but the other ingredients are unlikely to cause a urticaria, contact urticaria, dermatographism, of some patients developing upper airway and reaction.9 Despite our patient’s history of a single pressure urticaria, heat-induced urticaria, and cold- gastrointestinal swelling following endotracheal episode of contact urticaria, the diagnosis is not induced urticaria. intubation or esophagogastroduodenoscopy.2 The favored because the patient had only one treatment diagnosis of delayed pressure urticaria is made by using Lux Lotion® and two subsequent treatments Cold-induced urticaria provocation testing, by which pressure is applied without a skin protecting lotion, and she had similar Cold-induced urticaria is a common type to the skin for 15 minutes. The test is positive reactions after all treatments. of physical urticaria that usually occurs in if delayed-onset palpable swelling occurs. It is young adults and has a slight predominance in important to differentiate this from symptomatic Cholinergic urticaria females. Cold urticaria accounts for 6% to 34% dermatographism, which would have an immediate Cholinergic urticaria comprises about 30% of the 6 of physical urticarias. Triggers may include wheal-and-flare response. physical urticarias and has a higher prevalence cold air, cold liquid, ingestion of cold foods, or in young patients.10 This type of urticaria can be handling of cold objects. Symptoms usually occur The patient in this case did not present with pain induced by exercise, passive warming, emotional within minutes after exposure, but delayed types or any other symptoms outside of pruritus. Her stress, and hot or spicy food. The typical wheal-and- may take up to 24 hours.1 The skin reaction is symptoms occurred almost immediately following flare reaction lasts for 15 minutes to 60 minutes and typically localized to the area of contact; however, treatment, and it is unlikely that the laser head was is frequently localized to the trunk. The wheals are dangerous systemic reactions may occur after applied to any one location long enough to cause usually pruritic, numerous, and start very small but extensive cold exposure. The pathogenesis of cold delayed pressure urticaria. may coalesce.2 induced urticaria is unclear, it has been suggested that IgE antibodies may react to skin antigens Dermatographism Cholinergic urticaria often coexists with other at certain temperatures, which then causes the Also known as urticaria factitia (UF), physical urticarias, most commonly cold urticaria release of inflammatory mediators.6 dermatographism is the most common subtype of and dermatographism. In a retrospective study physical urticaria. It is often associated with skin of 92 male patients with cholinergic urticaria, Certain lasers use a cooling mechanism to reduce conditions like atopic dermatitis and idiopathic 3.3% had comorbid cold urticaria, and 6.5% had the heat accumulation in the epidermis, which urticaria and may also coexist with other physical comorbid dermatographism.10 These patients also reduces damage to the surrounding skin and aids urticarias. This condition is characterized by the had an elevated prevalence of allergic rhinitis and in patient comfort.3 Commonly used cooling development of a wheal-and-flare reaction that atopic dermatitis. In another study of 220 patients methods are gel cooling, cryogen cooling, forced occurs within seconds to minutes after shearing with cold urticaria, 8% had cholinergic urticaria.11 air cooling, and contact cooling. Cryogen cooling forces are applied to the skin, such as those associated The diagnosis of cholinergic urticaria is confirmed spray may result in transient erythema and mild with mild rubbing, stroking, or scratching.1 by provocation testing. It is also important to rule urticaria; one study showed transient urticaria one Dermatographism is divided into two variants: out exercise-induced anaphylaxis, a much more hour to 24 hours after exposure to cryogen cooling simple and symptomatic. Simple dermatographism dangerous condition. A diagnosis of cholinergic spray in three of 27 subjects.7 The patient in our is more common and is characterized by non- urticaria due to passive warming of the skin is case had treatments with both the LightSheer® pruritic urticarial welts that usually fade within possible in our patient; however, lack of prior diode 805-nm laser and the Vectus® diode 810- 15 minutes to 30 minutes. Symptomatic cholinergic urticaria and a symptom duration of nm laser, both of which utilize contact cooling dermatographism causes pruritic welts that can more than one hour make it less likely.

LASER-INDUCED URTICARIA: A CASE REPORT AND REVIEW OF PHYSICAL URTICARIA Solar urticaria References Solar urticaria, another rare subtype of physical 1. Abajian M, Młynek A, Maurer M. urticaria, occurs after exposure to ultraviolet (UV) Physical urticaria. Curr Allergy Asthma Rep. and/or visible light. Symptoms occur within five 2012;12(4):281-7. minutes to 15 minutes following exposure and usually resolve within 24 hours. Within the UV 2. Magerl M, Altrichter S, Borzova E, et al. The spectrum, UVA is the most common trigger, 1 definition, diagnostic testing and management of followed by visible light and UVB. Solar urticaria is chronic inducible urticarias - update and revision predominant in females, occurs equally in all ethnic of the EAACI/GA(2) LEN/EDF/UNEV 2009 groups and skin types, and has a peak age of onset 1 consensus panel recommendations. Allergy. of 20 years to 40 years. Solar urticaria may have a 2016;71(6):780-802. spontaneous onset and may subside after months or years. One study of 87 patients showed complete 12 3. Bernstein EF. Severe urticaria after laser resolution in 25% of cases within 10 years. A treatment for hair reduction. Dermatol Surg. few cases of delayed-onset solar urticaria have 2010;36(1):147-51. been described, with symptom onset after more 1 than one hour and resolution after 24 hours. The 4. Landa N, Corrons N, Zabalza I, Azpiazu JL. pathogenesis is unknown, but it is thought to be Urticaria induced by laser epilation: a clinical and 12 IgE-mediated and chromophore-dependent. It is histopathological study with extended follow-up in important to distinguish solar urticaria from more 36 patients. Lasers Surg Med. 2012;44(5):384-9. common photodermatoses, such as polymorphic light eruption and porphyrias. 5. Moreno-Arias GA, Tiffon T, Marti T, Camps- Fresneda A. Urticaria vasculitis induced by Urticaria triggered only by specific light diode laser photo-epilation. Dermatol Surg. wavelengths has been described. In these cases, 2000;26(11):1082-3. solar UV light exposure may not induce a reaction, but phototherapy devices may.3 Montaudié et 6. Hochstadter EF, Ben-Shoshan M. Cold- al. reported a case of solar urticaria on the face induced urticaria: challenges in diagnosis and induced by 415-nm LED treatment for rosacea in management. BMJ Case Rep. 2013 Jul 8;2013. pii: a patient with no history of urticaria following sun bcr2013010441. doi: 10.1136/bcr-2013-010441. exposure.13 7. Datrice N, Ramirez-San-Juan J, Zhang R, et al. We suspect that solar urticaria is the subtype of Cutaneous effects of cryogen spray cooling on in vivo physical urticaria involved in our case, though we human skin. Dermatol Surg. 2006;32(8):1007-12. can’t definitively exclude all other subtypes. Our patient denied prior instances of solar urticaria or 8. McFadden J. Immunologic Contact urtication following previous laser treatments, but Urticaria. Immunol Allergy Clin North Am. it is possible our patient has a specific sensitivity 2014;34(1):157-67. to the 810-nm wavelength involved in this case. A provocation test using 810-nm light in a 9. Sheehan M, Mousdicas N, Zirwas M. Irritants controlled setting could be performed to confirm and Allergens. Comprehensive Dermatologic Drug this hypothesis. Therapy. 1st ed. Elsevier, 2013. p. 613-619.

Treatment 10. Kim JE, Eun YS, Park YM, et al. Clinical The first-line treatments for most of the physical characteristics of cholinergic urticaria in Korea. urticarias is avoidance of triggers and symptomatic Ann Dermatol. 2014;26(2):189-94. treatment with first- and second-generation H1- antihistamines. In recalcitrant cases, treatment with 11. Torabi B, Ben-Shoshan M. The association omalizumab has been reported to be beneficial.12 of cholinergic and cold-induced urticaria: In patients with laser-induced urticaria who wish diagnosis and management. BMJ Case Rep. 2015; to continue their laser hair removal treatments, doi:10.1136/bcr-2014-2052582015. pretreatment with corticosteroids has been recommended. In cases where complete avoidance 12. Goetze S, Elsner P. Solar urticaria. J Dtsch of a trigger is not possible, pretreatment with Dermatol Ges. 2015;13(12):1250-3. steroids can be considered.4 13. Montaudié H, Lacour JP, Rostain G, Duteil L, Conclusion Passeron T. Solar urticaria to visible light triggered Although rare, severe urticarial reactions by light-emitting diode therapy. J Am Acad following laser treatments can be bothersome and Dermatol. 2014;71(3):e74-5. uncomfortable for patients. Providers who perform laser treatments should be aware that laser-induced urticaria is a possible side effect. Laser-induced urticaria is a physical urticaria that is inducible and often reproducible by an external stimulus. Categorization of laser-induced urticaria into existing physical urticaria subtypes is challenging because of the multiple steps and variables involved in laser treatment. It is possible that laser-induced urticaria is a combination or even a synergism of multiple physical urticarias that varies case by case. Additional studies are needed to better understand the pathophysiology of laser-induced, severe urticarial reactions.

EDGAR, BUCKLAND, MILLER