Hydroa Vacciniforme and CrossMark E'= -~ - at o l 2004 ;43( 12). ==_ - ~ 3 1, d om id e inhi bits Iln::~ ct on and an tigen ,'::'0 s J Inves t Derma­ Rattanavala i Nltiyarom, MOd, Chanisada Wongpraparut, MD b,*

;:: - '~a t m e nt of actin ic ~ -=,:) 326- 8. KEYWORDS ~ - a Th alidomide • Hydroa vacciniforme • Epstein-Barr virus • Photosensitivity • Photodermatoses -_a.- :" aching hospi taL • Lymphoproliferative disorder. Solar urticaria • Phototherapy • Plasmaplleresis - :: - 278- 84 _ ,: F a! Thalidomidein ) - ;' : 3 108(4)467- 71 KEY POINTS ' -,: -".. th alidomid e for _ ~"- atol 200 1;42(4) • Hydroa vacciniforme (HV) is characterized by a vesiculopapular eruption and necrotic lesions that heal with varioliform scars.

- .~ -- ~ u ez - So t o L Tra­ • HV has been reported to be associated with latent Epstein-Barr virus infection, raising the possibil­ ,:;-- !ah domida. Estu ­ ity of increased risk of Iymphoproliferative malignancy, ~:: Rev Mex 1993 • The mainstay of therapy in HV is adequate photoprotection, • Solar urticaria (SU) is characterized by skin , swelling, and whealing immediately after sun -,-~:;. ' ~ s JP, Moncada8 exposure. • Treatments for SU include photoprotection, medical therapy, phototherapy, photochemotherapy, and plasmapheresis. .

,:;- ~en VV R. Use of ,e manifestations - - a eno l 2000;130(6) HYDROA VACCINIFORME eggs," a reference to the vesicular eruption. "Vacci­ =-'~ _ei s A, De-Lu cas­ niforme" means "poxlike" scar, which is character­ Hydroa vacciniforme (HV) is a rare photosensitivity --;:c -, 3 inthe trea tment istic of this condition when the lesions heal, disorder predominantly affecting children , It is - .r - S:cc Esp Oftal mo characterized by recurrent vesiculopapular eruptions that evolve into necrotic crusts and var­ Epidemiology ',~ j", Brigard D, Hu­ ; ::':; ,- c pruri go, J Am ioliform scars on sun-exposed areas, Latent The rarity of HV and lack of universally diagnostic >. - : 10-2, Epstein-Barr virus (EBV) infection has been sug­ criteria make the precise prevalence difficult to ., ical characterlS­ gested to have a role in the underlying pathogen­ establish, The estimated prevalence of HV is 0,34 esis, HV has clinically been classified into classic -:;~ i1 As ians : a case cases per 100,000 population,1 Although well -;;;-; ' 301 Lep rol 2013; HV and severe HV-like eruption , The latter, recognized globally, it predominantly affects Cau­ described in adults, may be associated with sys­ casians,2.3 A bimodal distribution has been temic symptoms and an increased risk of Iympho­ described with peaks presenting at ages 1 to 7 proliferative disorders, Classic HV tends to remit and 12 to 16 years, Several cases of adult-onset by adolescence or early adulthood, This disease classic HV have also been reported.3-5 The pro­ significantly affects quality of life, causing both portion of female to male patients varies depend­ psychosocial and emotional morbidity, ing on the studies, ranging from 1: 1 to 1:2,1-3 Male patients tend to have a later onset, longer History duration, and more severe symptoms than female HV was first reported by Bazin in 1862,1 The term patients, 1 Although HV is usually sporadic, familial "hydroa" possibly derives from the Greek for "water cases have also been noted 6

Discl osure Statement: No conflict of Interest, E " Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Ma hidol University, 2 Wang lang Road, Bang­ CI ~ koknoi, Bangkok 10700, Thailand, b Department of Dermatology, Faculty of Medici ne, Si riraj Hospital, Mahi­ en .:! dol University, 2 Wanglang Road , Bangkoknoi, Bangkok 10700, Thailand c ~ Corresponding author. c:; E-mail address: [email protected] Q,) ~-: Dermatol Clin 32 (2014) 345-353 ....E http://dx, doi, org/ 10, 1016/j,det,20 14,03,0 13 Q,) 0733 -8635/14/$ - see front matter © 2014 El sevier Inc. All rights reserved, "'C 346 Nitiyarom & Wongpraparut

Pathogenesis itching or stinging sensation within hours or days af­ eruptions may 2. .0::_ ter sun exposure. Subsequently, the lesions prog­ as fever, malaise The precise pathophysiology of HV remains un­ ress to ulceration with necrotic crusts, and mosquito bites, I, - :: known. Sunlight, especially A (UVA), is eventually heal over a period of 1 to 6 weeks with splenomegaly, __ _ known to play an important role, because the char­ varioliform atrophic scars (Fig. 2). The distribution abnormal liver 'l_ - ::­ acteristic lesions of HV can be reproduced after 7 10 tends to be symmetric. The eruptions typically thrombocytoper <' artificial UVA exposure - EBV infections may develop on sun-exposed areas, such as the face and colon have 22:: also playa role in the pathogenesis of the disease, and dorsal hands, in the summer. Unlike classic patients with S8. ,,-:: as EBV has been detected in the lymphocytic infil­ HV, the lesions of severe HV-like eruption are larger EBV-associateo -2 trate of HV lesions from both pediatric and adult and deeper; this variant occurs more commonly ir' and/or natural ~ ~ :­ patients. Elevated levels of EBV DNA copies in adults. The lesions are distributed extensively. the peripheral blood and EBV-encoded small nu­ including on sun-protected areas, and may not al­ Histology clear ribonucleic acid (EBER) in cutaneous lesions ways be associated with photosensitivity, 19,2.< have been fou nd in both classic HV and severe HV­ Histology of ea __ 11 13 Facial swelling is also common. Seasonal variatior like eruptions. - Thus, both conditions have is not observed in the severe form. Disfigurement of giosis, focal ke c: - _:: been suggested to be variants within the same dis­ the ears and nose, in addition to contracture of the '/ascular .1 - ease spectrum. Higher copies of EBV are associ­ fingers, has been reported.22 Heat may provoke the Intraepidermal .2 :; ­ ated with symptom severity and worse prognosis symptoms in some of these patients.3 crosis, and u lce~ ' .: for patients. 1

_a boratory Fin d ~ __

- '1 8 diagnosis is ~ =-. -gs and pathC£ -::­ ~ _. s picious cases :: .: - "S may be ce o;;. :..crphyria. AUt02"- ' :- : o9ss ed to excluce --:: _::Jus erythema: c 5_~ Fig, 1. A 5-year-old boy with hydroa vacciniforme pre­ Fig , 2. Atrophic poxlike scars on the right cheek of a - ay be checkec ,.- 3= senting with papules, vesicles, and necrotic lesions of 5-year-old boy with hydroa vacc iniforme after - :; e proposed :r:::- -­ the left cheek. (Courtesy of Tor Shwayder, MD, Henry 10 days of treatment. (Courtesy of Tor Shwayder, c: ,tiate the two 2"? Ford Hospita l, Detroit, MI.) MD, Henry Ford Hospita l, Detroit, MI.) -- e T-cell recep!(; - ;7: Hydroa Vaccin iforme and So lar Urticaria 347

'": - --:ours or days aI­ eruptions may have systemic manifestations, such Photobiological Evaluation I me lesions prog­ as fever, malaise, weig ht loss, hypersensitivity to Although most patients show increased sensitivity :: -.:-~ c crusts, and mosquito bites, lymphadenopathy, hepatomegaly, to UVA radiation, they may demonstrate normal . . to 6 weeks with splenomegaly, abdominal pain, headache, minimal erythema dose (MED) to UVA. Repetitive 2 . - he distribution abnormal liver function testing, leukopenia, and UVA doses have been found to provoke character­ ?"'~p t ions typicall y thrombocytopenia.,g Erosions in the esophagus istic lesions of HV 9 The action spectrum for induc­ E ~_c h as the face and colon have also been noted.26 Furthermore, tion of skin lesions ranges from 320 to 390 nm.B - ,,' Unlike classic patients with severe disease may progress to :: =ruption are larger EBV-associated malignancy, including T-cell Management , -Jre commonly in and/or natural killer celllymphoma.'2 ~ :..::ed extensively. An important part of therapeutic management is ~ and may not al­ Histology strict photoprotection, including sun avoidance, : - ::;;osensitivity. '9.z use of photoprotective clothing and a wide­ 3es.sonal variation Histology of early lesions reveals epidermal spon­ brimmed hat, and application of broad-spectrum giOSis, focal keratinocyte degeneration, and a peri­ ~ c ~I sfigurement of sunscreen with sun-protection factor higher than : :.-::ntracture of the vascular Iymphohistiocytic infiltrate. 30. Unfortunately, no treatment has been univer­ :::z: l ay provoke the Intraepidermal vesicles, confluent epidermal ne­ sally successful.:> Chloroquine, ~-carotene , dietary ~ "' · - · :S 3 crosis, and ulceration are demonstrated in older fish oils, prophylactic ultraviolet B (UVB), and psor­ : . " ment has been lesions. Both classic HV and the severe variant alen plus UVA (PUVA) have been effective in some ;:-:J :ations include share similar histology. 12 However, the severe cases while thalidomide, azathioprine, and cyclo­ ·:s-a:oconjunctivitis. form usually reveals a denser lymphocytic infiltrate sporine are of uncertain efficacy. In severe cases, with few atypical cells, which extend into the sub­ ~ j . eltis, and scler­ systemic corticosteroids can also be used. In 27 ~ =-: of patients in a cutaneous fat. Immunohistochemical study of cases of chronic EBV infection, antiviral therapy a.-e study also re­ the infiltrates usually demonstrates T-ceil-ex­ was reported to reduce the severity and frequency i:-:r thous stomatitis pressing cytotoxic molecules, such as T-cell intra­ of eruptions in a small case series. 29 Because of cellular antigen 1 and granzyme B. '2 Direct .: 7 ) of the patients. the potential risk of systemic lymphoma in patients immunofluorescence study is usually nonspecific. :- r 3ntly in severe with HV and chronic EBV infection, close moni­ : c ssic HV. Classic toring and systemic evaluation should be - -;:; adolescence or Differential Diagnosis considered. The negative impact on the quality of life in HV ; ,:-re HV-like erup­ Several conditions need to be considered in the patients is significant. Psychosocial and emotional -.gB( clinical course differential diagnosis. Erythropoietic protoporphy­ 22 impairment in HV patients results from the diSfigur­ ,=' e wi th age. ria and porphyria cutanea tarda can be differenti­ ing effect of scarring, and the necessity for sun ated by their characteristic porphyrin profiles. avoidance and consequent restriction of daily The vesicular form of polymorphous light eruption ~ - f gn disease with activities. 3 resolves without significant scarring. Actinic pru­ severe HV-like rigo most commonly occurs in Amerindians or mestizos (individuals with a mixed Amerindian SOLAR URTICARIA and European extraction). Antinuclear antibody Solar urticaria (SU) is a rare charac­ (ANA) panel and skin biopsy should differentiate terized by skin erythema, swelling, and whealing bullous systemic from HV. immediately after exposure to diverse wave­ Herpes simplex virus infection can be diagnosed lengths of sunlight. It is estimated that SU ac­ by viral culture, and contact dermatitis by the his­ counts for less than 1% of all causes of 3o 31 tory of exposure to contactants. urticaria. • SU most commonly develops in women in the third decade of life. Though uncom­ Laboratory Findings mon, ithas a profound effect on individual quality of life. The diagnosis is generally based on clinical find­ ings and pathognomonic histologic features. In History suspicious cases blood, urine, and stool porphy­ rins may be obtained to exclude cutaneous The term "solar urticaria" was first proposed by porphyria. Autoantibody evaluation may be as­ Duke in 1923 when he described a 43-year-old sessed to exclude the low possibility of cutaneous woman who developed itching, skin erythema, lupus erythematosus. Circulating EBV DNA load and edema while she was exposed to the sun dur­ 3 ~ r e right cheek of a may be cheCked in select cases. Previous reports ing outdoor swimming. :? In 1923, Wucherpfenning ,ac ciniforme after have proposed that the most useful test to differ­ demonstrated that different wavelengths of light ;) o f Tor Shwayder, entiate the two vari ants of HV is monoclonality of could produce urticarial lesions.32 In 1942, Rajka . " I.) the T-cell receptor genes. ;g,2B successfully reproduced urticarial lesions on 348 Nitiya rom & Wongpraparut

intradermal injection of an affected patient's serum Differential Diagnosis "esponse. T t :::: ': " :;1i into a normal subject. 32 Subsequent information ; sographic a c "':- - :: The clinical manifestations of SU may reserr: ~ obtained from the serum transfer test helped to '1' m UVB to ' r~ 2 ' ",.: other photodermatoses. Detailed history, phys ­ clarify the pathogenesis of this condition. ;: " patients i F 2.-:::: examination, phototesting, and other inves ig;:­ ~ ~lI o n spec!r tions are essential in arriving at the diagnos s. Epidemiology Scotland, 4 '7: ::;.' =.= The onset of eruption within a few minutes of s J • Sible light '.'. ~ = :: ~ 1 exposure and the resolution within a few ho ~ 3J SU accounts for less than % of all causes of urti­ =- one. A slUG .. ' -;:;­ 31 caria.30. The prevalence of idiopathic SU in Tay­ are key in differentiating SU from polymorphc _-: :-9 most coml ~ r ::: : " light eruption. Erythropoietic protoporphy =­ side, Scotland was reported to be 3.1 per 2 ' UVA and lis t:; ;:: 33 100,000. The frequency of SU in photodermatol­ which may present with urticarial lesions follolt. -; :: on e and ther _ = exposure to sunlight , can be differentiated b_ : 0 ogy referral centers worldwide ranges from 1 % to : _Ilmon actio s::: =. ~· 18%.34.35 characteristic elevation of protoporphyrin in b J­ -2 t, followed ::: . :: • logical specimens. Systemic lupus erythematos_:: : ' 0 UVA ana :: can be differentiated by ANA panel, and lesions :-­ Clinical Manifestations -=- gapore de 0-0; ' ,," chronic idiopathic urticaria develop without a' -= oed urticari a .- ~:: : Patients with SU characteristically develop urticar­ correlation with sun exposure. Chronic ac -.:. :: Jn e. 31.3" The - ' '''--'0."7­ iallesions within 5 to 10 minutes of exposure to the dermatitis characteristically presents with licher ~­ ~ :an ces, preclp :,;."= sun; the lesions resolve within 24 hours, usually cation on sun-exposed areas. HV heals with SCc -~ 2:3f1 ceS differer-: ,,: : ­ within 1 to 3 hours. In addition to pruritus, ery­ Actinic prurigo mainly occurs in Amerindians c'': thema, and edema of the skin, patients may also :. ' esent a challe- ~ '" :: mestizos, presenting with persistent papule: ; ", 'lerate heat. - " 9 experience systemic symptoms, such as nausea, cheilitis, and conjunctivitis - 2.y be due to :- ~ dizziness, headache, wheezing, syncope, or, :; e tifying the c:: -. , rarely, anaphylactic shock.32.36 Whereas most pa­ Pathogenesis and Classification . 9 t will allow 2.- • tients develop lesions during direct sun exposure, : -,otoprotectio' a minority of patients only develop urticarial le­ SU results from a type I hypersensitivity reac i ­ sions immediately or a few minutes after returning Once skin is exposed to sunlight, a previous to the shade. This latter group was found to have a inactive cutaneous chromophore is likely CC'" ­ specific portion of sunlight that acts as an inhibi­ verted to a photoallergen. The photoallergen thr tion spectrum. SU commonly affects the upper interacts with immunoglobulin E (lgE)-spec : =.3c tion after s - ? • chest, arms, and forearms, whereas areas that mast cells, causing mast-cell degranulation c':' :".'1li ght. This ore-: are regularly exposed to the sun , such as the clinically apparent wheal and flare. '- e theory of inr t : _ face and hands, are infrequently involved. In highly Studies in the past with passive transfer tes: :: ee n reported I " -:; sensitive patients, SU may occur in covered areas currently considered unethical, have provided s ;:: ­ " "S described • " ~ " 3G of skin via light penetration through thin ciothing nificant information on the pathogenesis of S ~ ' -~ s landmar ,:,_ In addition, there is a rare and less severe form This procedure involves intradermal injection 'C ' Jman who de. =:: ~ of SU called fixed solar urticaria (FSU). In these pa­ an affected patient's serum into the skin 0 2. . :he range of .: :: -:: ­ tients, the wheals develop exclusively in a fixed normal subject, followed by irradiation with _ '3S inhibited b\ ­ area of skin and can be reproduced only at the causative wavelengths. The reverse passive tra s­ s:cectrum longe" "-.=. same site. To date, only 7 patients with this condi­ fer test involves irradiation of the skin of a heal ::- -otobiologica! s:.-:: 37 tion have been reported. -41 Recently Wessen­ individual, followed by injection of serum from t1- ? _-=o an, the i it ~: ­ dort and colleagues41 reported a case of affected patient. ::8% of patients.:' ­ delayed-onset FSU, with urticarial wheal develop­ According to Leenutaphong and colleagues. : ' ~ he inhibitio s::s­ ment 6 hours after ultraviolet exposure. The path­ SU is classified into 2 types. In type I, the patie '- e action spec;r", ­ ogenesis of FSU has not been elucidated, but may demonstrates an IgE-mediated hypersensitivity -':' " 1 spectrum is _-: " involve a difference in mast-cell population and specific photoallergens, which are present only , ~ es have bee- :: distribution in the skin. 4o patients with SUo A patient who has type I SU y-, ,,:'3b il ization, ph:"- :o have a variably positive passive transfer test and :: -,e IgE blockace ::: ­ Associated Conditions negative reverse passive transfer test. In type ?'gen and Ig E ~ ~. SU, the patient has abnormallgE antibodies again,," SU usually occurs in healthy individuals, but has a normal chromophore. Patients with type" SU w been reported to coexist with other photoderma­ always have a positive passive transfer test and :: toses such as polymorphous light eruption, variable or negative reverse passive transfer test. chronic actinic dermatitis, actinic prurigo, and 42 porphyria cutanea tarda. - 44 Medications, Action Spectrum including benoxaprofen, repirinast, oral contra­ ceptive pills, and tetracycline, have also been re­ The action spectrum in SU refers to the specific ported to induce SU-like reactions. 3G.45-J7 wavelength that can produce an urticari2. =so reported e ~ -:­ --

~ - ---..;;

Hydroa Vaccinif orme and Solar Urticaria 349

response, The action spectrum of SU varies by irradiation of the augmentation spectrum follOwing geographic and ethnic background, and can range exposure to the action spectrum, and proposed s~ from UVB to infrared wavelength,36,49 In a study of that the augmentation spectrum may amplify pro­ 61 patients in France, UVA was the most common duction of photoallergen after irradiation. action spectrum, 50 In a study of 84 patients in Scotland , 41 % of patients reacted to UVA and Photobiological Evaluation visible light while 30,9% reacted to visible light The purpose of phototesting in patients with SU is alone, 33 A study from Belgium demonstrated that =-: - DolymorphoL. s to identify the action spectrum of minimal urticarial the most common action spectra were UVA alone dose (MUD). Assessment of the phototest sites -otoporphyra or UVA and visible light, followed by visible light -..=. 2510ns followtr; should be done immediately after irradiation, and alone and then UVB alone, In Asians, the most ideally up to 1 hour after, The light sources for pho­ ="""rentiated by ':5 common action spectrum appears to be visible totesting should include UVA, broadband UVB, and ~:xrp h yrin in bio­ light, followed by a combination of visible light visible light (usually a slide projector). To eliminate .=: _5 erythematosl.. s and UVA and UVB, Studies from Japan and ~~ :: . and lesions c' the heat generated by a visible light source, a water Singapore demonstrated that most patients devel­ filter should be placed between the light source and 1:::- . =:):) wi thout ar oped urticarial reactions from visible light r~ :::nronic actinl_ the irradiated si tes, Fig. 3 illustrates an urticarial re­ alone, 31 ,36 The infrared spectrum can, in rare in­ action after visible light exposure. If phototesting re­ ~s.= - : s with lichenii,­ stances, precipitate SU; however, in such in­ r -9a ls with scars. sults are negative but SU is still suspected, natural stances differentiation from heat urticaria could sunlight exposure should be considered , In addi­ - :... - erindians a r ~c present a challenge because infrared is known to :.=0-;;. s;ent papules, tion, FSU should be considered in patients with generate heat. The wide range of action spectra recurrent urticarial lesions in a specified area, For may be due to the diversity of photoallergens. FSU , phototesting wi ll only be positive if performed Identifying the action spectrum for SU in each pa­ on the previously affected site. tient will allow an individualized treatment plan for As appropriate, serum ANA and porphyrin c:o.= - sirivi ty reactior. photoprotection. analyses should be carried out to exclude lupus r ; , ;. a previousl: erythematosus and porphyrias. Inhibition Spectrum c'= 's likely cor ­ I ::-'-'oioallergen ther Some patients with SU display a delayed urticarial Management - :: (lgE)-specilic reaction after sun exposure but not while in direct There are several treatment options for SU , ssyranulation anc sunlight. This phenomenon can be explained by including photoprotection, medical therapy, photo­ c-e_ the theory of inhibition spectrum, which has mainly therapy, photochemotherapy, and plasmaphe­ ~ ,e transfer tes:. been reported in the Japanese literature and was resis. As many patients with SU are sensitive to -:: . e provided sig­ first described in 1982 by Hasei and Ichihashi. f> ' visible light, sunscreens alone are not particularly ~ - ~ enesis of SU This landmark study reported a 42-year-old efficacious, In severe cases, a combination of ~ = -, a l injection 0' woman who developed urticaria from visible light several treatment modalities should be considered. - ::' the skin of 2. in the range of 400 to 500 nm, but this reaction :;.:::.ation with the was inhibited by immediate re-irradiation wi th a Medical therapy '=-'Se passive trans­ spectrum longer than 530 nm. In a clinical and Antihistamines H1-receptor antagonists are the -=s-

development of SUo H1 antagonists that have melanocortin-1 receptor. Exogenous ad minis: c ' been reported to effectively control this condition tion of this agent increases melanization ia : -~ are hydroxyzine, astemizole, terfenadine, cetiri­ melanogenesis pathway. A recent study p :: . zine, and fexofenadine.32 However, astemizole li shed in the United Kingdom demonstrated ­ and terfenadine have been withdrawn from the tential benefits of a-MSH analogue for S_ ~ ~ J -1 .'.ee s c..- ~ -- .: market because of the risk of cardiogenic toxicity. patients'" Five patients with SU received a si g '= -~ r :e 'or : ~ ~=-- :o ­ Cimetidine, an H2-receptor antagonist, and doxe­ dose of 16 mg afamelanotide implant subcutar:­ - :); .I" S. pin, an H1 /H2-receptor antagonist. have also been ously during the winter months. The investigate _ :l a"Smaphere; s -'-;;; ­ reported to control this condition. 57.58 found that following day 7 after implantation ' -,,­ melanin index progressively increased, peak,"; : - ange r 2 ' C-;O ~ . -~ Cyclosporine Cyclosporine was effectively used at 15 days and persisting until 60 days. .:, . in one recalcitrant case of SU. At a dose of --;:, '" SU pa: ", - : ,:, - ::­ 60 days postimplantation, the MUD \"c~ 4.5 mg/kg/d of cyclosporine, the patient tolerated ::2:e. ---:' S '. -:; ' :- " increased in comparison with baseline, a l o r~ 1 hour of sunlight compared with only a few mi­ : -'" therapy: ..: -2..:: with Significantly decreased whealing. 71 Afame 2­ nutes previously. However, the wheals recurred : ;, eeks. arc '- " :. '­ notide is also currently under investigation for t ~ 59 ',' ~ st patler. ·s I - _ • after the drug was discontinued. Cyclosporine treatment of erythropoietic protoporphyr;: may be an option for patients who live in countries - ~ : had a ~-= ~ : Although it may be a promising therapeutic 0;:­ -­ with short summer months. tion for SU in the future, the potential risk c -:>r ognosis Methotrexate Although the use of methotrexate dysplastic nevi and melanoma from this ne,' for SU has not been reported, it is an established agent, which has not been observed thus 2 ­ o~ -- -­ treatment for recalcitrant chronic urticaria. GO should also be taken into consideration. --g-terrn a. "- -:~ ~~­ Therefore, in resistant cases of SU it is reasonable :-33rrnens. e ' 7--~ to use methotrexate as another treatment option. Procedural therapy .:' soontanec _s ""­ Phototherapy and photochemotherapy T ~ SJ the pr bE.: Intravenous immunoglobulin Intravenous immu­ concept of induction of a tolerant state or "har . ::": · : .an ":' 6: _ 2:: noglobulin (IVIG) is a blood product containing ening" by the causative wavelength may be use: -~cSJe c l iv e t,. - - ::C ' ; polyvalent immunoglobulin G. Through its immu­ to treat various photosensitive diseases, includir ; -:. .' ea rs and ,', -:- : nomodulatory effects, IVIG has demonstrated effi­ SUo Phototherapy for SU may involve either th, - ~. e a \' ors", L'':'", __ cacy in the treatment of various types of traditional non-rush-hardening or newer rus ­ recalcitrant urticaria, such as chronic, autoim­ hardening protocols. The non-rush-hardenln;; 61 -EFERENCES mune, and delayed pressure, as well as SU. -65 technique uses the action spectrum identified b, A survey conducted of French photodermatology phototesting to induce wheali ng of the skin, starl­ units reported that 5 of 7 patients with SU who ing lower than the minimal whealing dose (M WO were treated with IVIG obtained complete remis­ and gradually increasing the dose. The frequenc sion. The IVIG doses are in the range of 1.4 to is 2 to 4 times per week. A drawback of thi.: 2.5 g/kg with infusion over 2 to 5 days. The number method is the very short period of remission. of courses varies from 1 to 3, with time between in­ Compared with phototherapy, photochemother­ fusions typically 2 to 9 months. Remission was apy (P UVA) provides longer-lasting effects. 73 32C--: maintained for a duration from 4 months to more The rush-hardening protocol is used for rapic than a year.66 IVIG is generally safe; however, it tolerance to light. UVA rush hardening is per­ has been associated with an increased risk of viral formed by exposing the patient to half of the infections and anaphylaxis. MWD of UVA to a quadrant and then to half 0' Omalizumab Omalizumab is a recombinant hu­ the body at increasing doses of UVA at 1-hour in­ tervals over 2 to 3 days.74,r With this technique P r: ~ :: manized monoclonal anti-lgE antibody primarily -- Je e: indicated for the treatment of asthma. Recently the patient will gain a higher MWD within severa there have been several reports of successful use days. Maintenance UVA irradiations are scheduleo of omalizumab for recalcitrant chronic urticaria, every 1 to 2 weeks. Remissions for at leas: 67 70 5 months to 1 year have been reported after treat­ , , and SU. ­ ment with the UVA rush-hardening 200 ' . ..: ..: .: ~ -­ The dosage of omalizumab ranges from 150 mg protocoI. 74.--~ _ 3~p;a G '. every 2 weeks to 150 to 300 mg per month. Omalizu­ Finally, wavelengths outside the action spectra mab may be an option for SU patients with elevated may induce tolerance. Recently, narrow-bano levels of IgE who fail other treatment modalities. UVB as an inhibition spectrum was successfull . -- "'aasz used in a patient with SU who had the action spec­ et.-Melanocyte stimulating hormone analogue trum in the UVA and visible-light range. 76 a-Melanocyte stimulating hormone (C1,-MSH) At the Phototherapy Unit at Henry Ford Hospital - 30nnex 4 analogue, also known as afamelanotide, [Nle -D­ in Detroit, Michigan, a variation of rush hardening • f':'h ~, -~. ­ Phe7]-a-MSH, is a super-potent agonist of the with UVA is commonly performed, with success. ·Ci-S. Hydroa Vacciniforme and Solar Urticaria 351

.:.;s"ous administra­ The protocol involves exposing the patient to 50% 9. Sunohara A, Mizuno N, Sakai M, et al. Action spec­ - ,;; " lization via tt- ~ of MWD of UVA, and increasing it by 10% to 20% trum for UV erythema and reproduction 01 the sk in -S::9nt study puc­ as tolerated 3 times per week for a total of 30 treat­ leSions in hydroa vacciniforme Photodermatol - c 9monstrated pc ­ ments. Tapering then follows to 2 times weekly for 1988;5(3} 139-45. -:: ,alogue for SL 3 to 4 weeks, and then to once weekly as mainte­ 10 Wisuthsarewong W, Leenutaphong V, Viravan S. ~_ -eceived a sing-= nance for the remaining duration of the summer Hydroa vacciniforme with ocular Invo lvement. ::: ~0 l ant subcutars ­ months. J Med Assoc 1hai 1998;81( 10}807-11 - 5 , - he investigators 11 . Iwatsuki K, Oht suka M. Akiba H, et al. Atyp ical hy­ Plasmapheresis As the pathogenesis of SU likely -=:' :np lantation th= droa vacciniforme in Childhood: from a smolderin g implicates a photoallergen, removal via plasma ex­ - : -eased, peakir;; stage to Epstein-Barr virus-associated lymphOid change may be a therapeutic option. Ten recalci­ _~ j l 60 days. A: malignancy. J Am Acad Dermatol 1999;40(2 Pt 1} trant SU patients have received this procedure to : -e MUD wa~ 283-4. date.n--a3 Six of the patients responded well to ~ oaseline, alo l ~ 12. Iwatsuki K, Satoh M, Yamamoto T, et al. Pathogeni c the therapy; 4 had remission, 1 had relapse at -,=~ li n g. 71 Afamela­ link between hydroa vacciniforme and Epstein-Barr 2 weeks, and the other had relapse at 2 months. -, estlgation for the virus-associated hematologic disorders. Arch Der­ Most patients who responded well to the treat­ orotoporphyria matoI2006;142(5)587-95. ment had a positive serum factor. E - ,;::; :herapeutic op­ 13. Ve rneu il L, Gouarin S, Comoz F, et al. Epstein-Barr ~ - ~ ootential risk 0' virus involvement In th e pathogenesis of hydroa Prognosis C - E from this ne\'. vacciniforme: an assessment of seven adult pa­ c.')5erved thus far. SU is a chronic condition. Most patients require ti ents with long-term follow-up. Br J Dermatol - ~~ eration. long-term antihistamines and/or combination 2010; 163( 1) 174- 82 treatments. Nevertheless, there have b een reports 14. Au WY, Pang A Choy C, et al. Quantifi cati on of of spontaneous remission over time. For solitary circulatin g Epstein-Barr virus (EBV) DNA in the chemotherapy The SU, the probability of clinical resolution is 15%, diagnosis and monitoring of natural killer cell and .': " ": state or "hard­ 24%, and 46% at 5, 10, and 15 years from onset, EBV-positive lymphomas in immunocompetent pa­ Eo : - ;,Jih may be used respectively. 33 Patients who are older than tient s. Blood 2004; 104( 1} 243-9 _ J :::eases, including 40 years and with long duration of disease activity 15. Gotoh K, Ito Y. Shibata-Watanabe Y, et al. C!inical ~ . "'i'lolve either the have a worse prognosis. 33 and VIrological characteristics of 15 patients w:t h - = :x newer rush­ chronic active Epstein-Barr viru s :niec:ion treated - ::: r - ru sh -hardening REFERENCES with hematopoietic steM c e l ~ trar sp 2n ~ 2: i c .1. Clln : -:- : :- _, m identified by Infect DIS 20 G8 ;46{10) 1525-34 -,; of the skin, start­ Gupta G, Man I. Kemmett D. Hydroa vacciniforme 16. Kimu ra H. Pathogenesis of cho:llc aC' IV e E::-ste.n­

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