Baraldi C.

Chessa M. A.

Filippi F.

Misciali C.

Neri I.

Patrizi A.

Sechi A.

Virdi A.

English

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lable at ScienceDirectAllergology International 69 (2020) 645e647Contents lists avaiAllergology Internationaljournal homepage: ht tp: / /www.elsevier .com/locate/al i tLetter to the EditorLocalized cold urticaria after vaccination in a child: A case and literaturereviewDear Editor,Cold urticaria (CU), the second most frequent type of chronicinducible urticaria, is characterized by skin lesions and/or angioe-dema developing upon contact with cold air, liquids or solids, sub-sequent to the release of proinflammatory mast cell mediators onexposure to low temperatures.1 CU can be subdivided into familialor acquired forms. The latter can be classified as primary or second-ary to an underlying cause, such as infections (mainly viral patho-gens), cryoglobulinemia, hypersensitivity vasculitis, drugs,neoplasms. Certain acquired CU (ACU), called atypical ACU syn-dromes, could not exhibit wheal formation after standard cold con-tact stimulation tests, and consequently their diagnosis mustdepend on history and other diagnostic procedures. Among them,have been included the systemic ACU, the cold-dependent derma-tographism, the cold-induced cholinergic urticaria, the delayedcold urticaria, the localized cold reflex urticaria and the localizedcold urticaria (LCU). In particular, LCU is defined by clinical manifes-tations only in a specific body area (sites of immunization/desensi-tization, site of insect bites or idiopathic).2,3Here we describe a unique case of LCU at the site of vaccine in-jection in a paediatric patient.A 6-year-old child was referred to us for a 6-month history of anasymptomatic annular wheal on the left upper arm, which regu-larly appeared a few minutes after direct or indirect cold exposure(local cold exposure, cold shower, cold exposure while wearingclothes) and disappeared spontaneously after 30e60 min.The lesion occurred in the site of injection of the first dose ofMeningococcal B vaccine (Bexsero, GlaxoSmithKline Vaccines),one month after its administration. Similar lesions had not beennoted elsewhere in his body and no systemic symptoms or angioe-dema occurred during the attacks. The patient had not history ofatopy or recent infections. Complete blood test exam, includingC-reactive protein, C3 and C4, cryoglobulin, total IgE, autoimmuneand viral serology (EpsteineBarr virus, hepatitis B and C virus)panel showed normal results. At first examination no cutaneous le-sions were present (Fig. 1a), so we performed an ice-cube test (ICT)and after 2 min the expected annular wheal appeared exactly in thesame area as the previous times (Fig. 1b), disappearing within 1 h(Fig. 1c). Darier sign was negative at the vaccine administrationsite where the wheal appeared. Results of ICT on other body areasfailed to induce lesions. Curiously, the urticarial rash had notoccurred in the other arm, where the vaccine recall was performed3 months after the first dose, even after ICT.Peer review under responsibility of Japanese Society of Allergology.https://doi.org/10.1016/j.alit.2020.04.0131323-8930/Copyright © 2020, Japanese Society of Allergology. Production and hosting by Elselicenses/by-nc-nd/4.0/).Echotomography, performed 1 h after ICT, showed an ill-definedisoechoic oedema of soft tissues, extending from the deep dermis tothe subcutaneous tissue. The Color Doppler modality did not detectincreased vascular signals. Based on these findings, vaccine-induced granuloma was ruled out, since it usually appears as hypo-echoic and well structured4 (Fig. 1d).We performed a punch biopsy from the annular wheal somemi-nutes after inducing it and microscopic examination showedoedema, a sparse slight-moderate perivascular superficial, deep,interstitial mixed inflammatory infiltrate, predominantly consist-ing of lymphocytes, rare eosinophils, neutrophils and mastocytesbetween collagen bundles in the dermis (Fig. 1e). C-KIT(CD117)staining showed just few mastocytes in the dermis (Fig. 1f).5Histological and immunocytochemical features were consistentwith early stage urticaria.To our knowledge, this is the first case of LCU induced by vaccineinjection.In fact, we are able to find only two different situations reportedin the literature: (a) 4 cases of CU following vaccination and (b) 4cases of LCU associated with immunotherapy (Table 1).More precisely, in 4 cases CU occurred after vaccine injections: in3 cases the wheals were localized on cold air-exposed areas, whilethe fourth experienced generalized urticaria and angioedema;none of them had cutaneous manifestations restricted to the siteof injectiononly. In these cases, sincedifferent vaccineswere incrim-inated, an immune allergic reaction to the vaccine viral strain itselfand subsequent mast cell activationwas suspected by the authors.6On the other hand, in 4 cases the LCUwas strictly confined to thesite of subcutaneous immunotherapy (tree pollen extract) in pa-tients with seasonal allergic rhinocojunctivitis. ICT resultedstrongly positive in the area of administration and negative in therest of the body.7e9We hypothesized that in our case the pathogenetic mechanismunderlying the clinical manifestations was more similar to theforms of LCU induced by immunotherapy: a local (immunologicor not) tissue injury which triggers a delayed cold-inducedhypersensitivity.In our young patient, we prescribed oral antihistamines (cetiri-zine 10 mg/day) with partial remission of his local symptoms.In conclusion, we reported the first case of LCU developing aftera vaccine injection in a child. Interestingly, the cutaneous manifes-tation has remained localized and no other symptoms have beenreported even 6 month later.However, it may be prudent to follow-up young patients withLCU for possible progression to systemic manifestation, includinganaphylaxis, and keep in mind that a history of recent vaccinationvier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/Fig. 1. No cutaneous lesion was present at first examination (a), occurrence of the annular wheal 2 min after performing the ice-cube test in the site of vaccination (b) and spon-taneous disappearance of the lesion after 1 h (c). Echotomography showed an ill-defined isoechoic oedema of soft tissues, extending from the deep dermis to the subcutaneoustissue (d). Microscopic examination showed oedema, a sparse slight perivascular superficial, deep, interstitial mixed inflammatory infiltrate, predominantly consisting of lympho-cytes, rare eosinophils, neutrophils and mastocytes between collagen bundles in the dermis (H&E, 44x) (e). C-KIT(CD117) staining revealed a few mastocytes around vessels ofsuperficial and deep dermis (36x) (f).Table 1Case reports of cold-induced urticaria after immunotherapy or vaccination.Reference Age Skin surface areainvolvedTrigger Time betweentrigger and onset ofsymptomsTest performed Therapy LaboratoristicabnormalitiesassociatedDucomunnet al., 200829 Localized (site of theinjections)Subcutaneousimmunotherapy (for treepollen allergy)During 2 year ofimmunotherapyIce-cube test: positivein few minutes only inthe site of injectionAntihistamines NoneSolomon LMet al., 1966e Localized (site of theinjections)Subcutaneousimmunotherapy (for treepollen allergy)e e e eGarcia F et al.,199829 Localized (site of theinjections)Subcutaneousimmunotherapy (forgramineous pollen allergy)During 2 year ofimmunotherapyIce-cube test: positivein few minutes only inthe site of injectionAntihistamines (no relapse atthe following dose)None36 Localized (site of theinjections)Subcutaneousimmunotherapy (forgramineous pollen allergy)During 4 year ofimmunotherapye Spontaneous remission in 6monthsNoneRaison-PeyronN et al., 20164 Cold-exposed areas Vaccination anti N.meningitis serotype C5 days aftervaccinationIce-cube test: positive Antihistamines þ montelukast None29 Cold-exposedareas þ angioedemaVaccination anti yellowfever and hepatitis A3 weeks aftervaccinationIce-cube test: positive Antihistamines None2 Cold-exposed areas Vaccination anti S.pneumoniae þ diphtheria,tetanus, poliomyelitis, H.influenzae B, pertussis7 days aftervaccinationIce-cube test: positive Antihistamines None37 Cold-exposed areas Vaccination anti H1N1influenza virus3 weeks aftervaccinationIce-cube test: positive Antihistamines þ prednisolone(no relapse at the followingdose)NoneLetter to the Editor / Allergology International 69 (2020) 645e647646should be investigated to properly diagnose this rare and curiousphenomenon.Conflict of interestThe authors have no conflict of interest to declare.Federica Filippi *, Andrea Sechi, Carlotta Baraldi, Cosimo Misciali,Annalisa Patrizi, Marco Adriano Chessa, Annalucia Virdi, Iria NeriDermatology Unit, Department of Experimental, Diagnostic and Specialty Medicine,University of Bologna, Bologna, Italy* Corresponding author. Dermatology Unit, Department of Experimental,Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 1, 40138,Bologna, Italy.E-mail address: federicafilippi8@gmail.com (F. Filippi).References1. Siebenhaar F, Weller K, Mlynek A, Magerl M, Altrichter S, Vieira Dos Santos R,et al. Acquired cold urticaria: clinical picture and update on diagnosis and treat-ment. Clin Exp Dermatol 2007;32:241e5.2. Wanderer AA, Hoffman HM. The spectrum of acquired and familial cold-induced ur-ticaria/urticaria-like syndromes. Immunol Allergy Clin North Am 2004;24:259e86.Letter to the Editor / Allergology International 69 (2020) 645e647 6473. Sciallis 2nd GF, Krych EH. Localized cold urticaria to the face in a pediatricpatient: a case report and literature review. Pediatr Dermatol 2010;27:266e9.4. Sechi A, Patrizi A, Vincenzi C, Savoia F, Tartari F, Leuzzi M, et al. Sonographic fea-tures of vaccination granulomas in children with delayed-type hypersensitivityto aluminum. Pediatr Dermatol 2019;36:1012e6.5. Church MK, Kolkhir P, Metz M, Maurer M. The role and relevance of mast cells inurticaria. Immunol Rev 2018;282:232e47.6. Raison-Peyron N, Philibert C, Bernard N, Du-Thanh A, Barbaud A, Bessis D. Coldcontact urticaria following vaccination: four cases. Acta Derm Venereol 2016;96:852e3.7. Ducommun J,MorelV, Ribi C,HauserC. Localized cold-inducedurticaria associatedwith specific immunotherapy for tree pollen allergy. Allergy 2008;63:789e90.8. García F, Blanco J, Perez R, Alonso L, Marcos M, Carretero P, et al. Localized coldurticaria associated with immunotherapy. Allergy 1998;53:110e1.9. Solomon LM, Strauss H, Leznoff A. Localized "secondary" cold urticaria. Arch Der-matol 1966;94:156e60.Received 5 January 2020Received in revised form 10 April 2020Accepted 21 April 2020Available online 30 May 2020

Localized cold urticaria after vaccination in a child: A case and literature review

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Localized cold urticaria after vaccination in a child: A case and literature review

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