Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Beijing, This isan open access article under the CC BY-NC license.www.medicaljournals.se/acta W Corr: Acta DermVenereol 2019;99:953–959. Accepted Jul17,2019;E-published2019 eccrine carcinoma;lichensclerosusetatrophicus. Key words: nancies. diseases inWolf’s isotopic especially response, malig considerthe possibilitiesclinicians should different of ter-associated Wolf’sisotopic Additionally, response. zos herpes for categories classification response pic sponse Wolf’s impetigo. to isoto Wesuggest include it hasextended thespectrumof Wolf’s isotopic re sponse following herpeszoster infection; moreover, re isotopic Wolf’s confirmed with patients additional sinophils, andtumourOur studyhasdescribed cells. inthe lesions.CD4 changes tients allowed exploration ofsecondary microscopic in 10pa analyses tients andimmunohistochemical Histopathologicalcarcinoma. examinations in 12 pa to disease inflammatory from ranging manifestations se after herpes zoster infection, as which presented 1 Tao of 24NewCasesandLiterature Review Wolf’s IsotopicResponse after HerpesZoster Infection:AStudy minimal changesbythefirst disease’. ‘, pigment changes, colour changes or various other trigger an isotopic response; the definition now includes that diseases skin healed of definition the expanded (2) al. et Wolfcommentary, recent a In (4–6). literature the in reported been have reactions WIR cutaneous at a site with damaged or traumatised skin (2, 3). Many disease same the of development the describes which – phenomenon Köebner the as known also – response isomorphic and WIR of definitions the surrounded has controversy recently, Until (1). WIR for definition precise a established and phenomenon dermatological this recognised al. Wolfet healed. previously had that disorder skin unrelated an of site exact the at disorder study included 24patients withstudy included Wolf’s isotopic respon This afterherpeszoster.lesions havebeendescribed disease that hadpreviously healed.Various cutaneous skindiseaseattheexactsiteof anunrelatedskin new Wolf’s isotopic refersto response ofthe a occurrence normal and infiltrating cells included mast cells, eo cells, mast included cells infiltrating and normal Chaoyang District, Beijing, and Beijing, Chaoyang District, a Clee N. Sui u un Dnceg itit Biig 100730, Beijing China. E-mail:[email protected] District, Dongcheng Yuan, Fu Shuai 1 No. College, cal lege Hospital, Chinese Academy of Medical Sciences & Peking Union Medi- Journal Compilation ©2019ActaDermato-Venereologica. Department of Dermatology,PekingUnionMedicalCollege Hospital, Chinese Academy of MedicalSciences& PekingUnion Medical College, WANG Yuehua LIU, Department of Dermatology, Peking Union Medical Col in 1955 and refers to the occurrence of a new skin olf’s isotopic response (WIR) was first described 2 Department of Dermatology, Chengdu Second People’s Hospital, Sichuan, 1 , Wolf’s isotopic response; herpes zoster; syringoid Min ZHANG 2 , Ying ZHANG 4 Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine AffiliatedHospital, Tianjin,China + /CD8 + T-cellratios were 3 , Yu ZHANG CLINICAL REPORT 4 , Shiyu ZHANG ------

various theories have been proposed to explain this phe this explain to proposed been have theories various pathogenesis of WIR after HPZ remains unclear, although response’, has been suggested by several authors (8). The isotopic ‘Wolf’spostherpetic term, new a and (7), WIR thus, HPZ is the most common primary disease to induce WIR; as described been have HPZ healed of site the at spreads down the sensory nerve. Many cutaneous lesions virus the as intensifies which neuralgia, severe in result can necrosis and inflammation Neuronal ganglionitis. painful produces and ganglion root affecteddorsal the in replicate to continues virus the outbreak, HPZ an During varicella. of attack earlier an following ganglia sensory virus (VZV) infection which persisted in latent form within varicella-zoster endogenous an of reactivation the from led in this study. Patients’ clinical medical histories were obtained Twenty-four patients with cutaneous lesions after HPZ were enrol Clinical specimens MATERIALS ANDMETHODS inflammatory infiltration,andmalignantinvasion. changes, epidermal including WIR, of review literature gical features of WIR. In addition, we conducted a concise clinical manifestations and explored the dermatopatholo 24 patients who had WIR after HPZ. We characterised the fication and investigation. In the present study, we enrolled of this clinical phenomenon, and it requires further classi be the most widely accepted. There are several descriptions hypotheses, as well as a neural hypothesis (6), which may nomenon; these include viral, vascular, and immunologic the possibility of associated tumorousdiseases. especially phenomenon, this of aware be to reminded are paper,this in clinicians study the Through WIR. in vasions in malignant and infiltrations inflammatory changes, sue tis dermal changes, follicular and epidermal the findings, pathological on based method classification a propose and impairment neuro-immune by caused WIR that pothesis and histopathological study in this study, we tend to a hy first described disease. Based on the mini literature review after herpes zoster were enrolled inthisstudyincluding cal concept. Twenty-four new patients presented with WIR Wolf’s isotopic response (WIR) is widely accepted as a clini SIGNIFICANCE Herpes zoster (HPZ) is a localised disease that results results that disease localised a is (HPZ) zoster Herpes 1 , Tao QU 3 Department of Dermatology, Shuangqiao Hospital of 1 , Yuehua LIU Acta DermVenereol 2019;99: 953-959 1 andHongzhongJIN doi: 10.2340/00015555-3269 1 953 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta ANA: antinuclear antibody; Interval: interval betweenWolf’s isotopic response andherpes zoster; NA: noneapparent; ND: not done. Table I.Clinicalandhistopathologicalcharacteristicsofthe24patientsinthisstudy describing relevanthistopathologicalchangeswerereviewed. reports, and letters to the editor mentioning this phenomenon and case series, case reviews, English. All in abstracts or English in written publications to restricted was literature the of selection response’, ‘isotopic response’, and ‘herpes zoster’. The search and ‘Wolf’skeywords: the using Embase and PubMed from isotopic obtained was 2018 to 1987 from published literature Relevant WIR. regarding data collect to search literature Wea performed Literature review and writtenconsentwasobtainedwhenpatientswerebiopsied. ethical statements were obtained when patients were photographed, Informed consent was obtained from all patients. Oral or written Ethics nose thetumour. diag to staining immunohistopathological additional underwent 20 Patient (9). CD117 or CD8, CD4, for staining no with tissue China), whereas slides for patient 11 showed only stained elastic Beijing, Euroimmun, (ELISA; 230 and BP180 antibodies test to immunofluorescence indirect and immunofluorescence direct was conducted for two patients. Patient 7 was only assessed using was conducted for 10 patients; CD138 (Leica Biosystems) staining systems, Shanghai, China) and CD117 (c-kit; Leica Biosystems), CD4 (Maxim Biotechnologies, Fuzhou, China), CD8 (Leica Bio for staining including staining, Immunohistochemical patients. 12 for performed were biopsies Skin patient. each for recorded also were HPZ to prior history medical and received, treatment if available. Age, sex, time interval between acute HPZ and biopsy, 954 12 16 11 24 20 15 10 21 23 22 19 18 17 14 13 No Pat. 9 8 7 6 5 4 3 2 1 65/M 46/M 24/M 23/F 61/F 39/F 78/F sex years/ Age, 74/M 44/F 61/F 29/F 52/M 61/F 26/F 45/F 79/M 64/F 50/F 33/F 35/M 58/F 52/F 64/F 57/F T. Wangetal. > 100 >100 (weeks) Interval > 100 > 100 8 16 12 12 24 6 6 52 12 20 12 16 5 8 20 4 3 3 26 12

Left earandneck Right forehead Left abdomen Right face Left back Right back and abdomen Location Left back Left chestandback Left chestandback Left abdomenandback Left chestandback Left back Right back and rib Left back Right chest and back Left neck Left chestand back Left abdomenandback Left backand abdomen Left chestand back Left face Right chest Right chest and back Right chest and back

NA NA NA NA Herpes zoster endocarditis Polymyositis; infectious mammary glands Hyperplasia of the Hypertension Sjogren’s syndrome NA ANA positive NA NA Urticaria lumbar spine Tuberculosis of the Past medicalhistory Prostate cancer; gout NA ovarian cancer Endometrial carcinoma; Sjogren’s syndrome NA Diabetes mellitus NA NA NA - - Lichen planus Comedones et atrophicus Acne vulgaris andcomedones Contact dermatitis Poikiloderma Lichen sclerosus et atrophicus Prurigo Psoriasis hyperpigmentation Postinflammatory Eosinophilic dermatitis Localized Lichen striatus Comedones Vitiligo Prurigo Bullous pemphigoid Keloid Psoriasis Dermatitis neglecta Impetigo Folliculitis and comedones Lichen planus Clinical diagnosis Table I, the time intervals between HPZ and the presen in shown shoulder.As and neck the on one and neck, respectively. 21, and 14, 13, 4, patients in found were hypertension mellitus, tuberculosis of the lumbar spine, urticaria, and but exhibited no definite rheumatoid diseases. Diabetes tient 19 had a positive antinuclear antibody (titre 1:160), various appearances. Twelve patients were patients Twelve appearances. various Clinically,patients’ exhibited manifestations cutaneous varied, ranging from 3 to > scars HPZ of sites the at reactions cutaneous of tations corticosteroids and/or immunosuppressive agents. Pa agents. immunosuppressive and/or corticosteroids patient 15); these 8 patients regularly received systemic in endocarditis infectious and polymyositis 23; and 6 patients in syndrome (Sjögren’s diseases autoimmune with 3 including diseases, chronic had patients Eight gout. Patient 10 had hyperplasia of the mammary glands. and cancer prostate with diagnosed been had 9 patient with endometrial carcinoma and ovarian diagnosed cancer, been whereas had 7 patient particular, in cancer; of history.medical noteworthy Twohistory a had patients 23–79 years (mean 50.8 years). Thirteen patients had of no range age an with men, 7 and women 17 including in shown are series our for findings Clinical RESULTS Nineteen lesions were on the trunk, 4 on the face and Lichen planus comedones Idiopathic dermatosis and Bullous ND eccrine carcinoma atrophicus andsyringoid Bullous lichen sclerosis et ND ND Lichen planopilaris ND Localized scleroderma ND Localized scleroderma atrophicus andcomedones Bullous lichen sclerosis et ND Keloid Histopathological findings ND ND Bullous pemphigoid ND ND ND ND Comedones Granulomatous dermatitis 100 weeks (mean 28.3 weeks). CD4 CD4 ND ND CD4 ND ND CD4 ND CD4 ND CD4 CD4 ND CD4 chemical findings Immunohisto­ CD117 ND ND ND ND ND ND ND CD4 CD4 CD138 CD138 + + + + + + + + + + , CD8 , CD8 , CD8 , CD8 , CD8 , CD8 , CD8 , CD8 , CD8 , CD8 + + – diagnosed , CD138 Table I, + + + + + + + + + + CD117 CD117 , , CD117 , CD117 , CD117 , CD117 , CD117 , CD117 , CD117 + + – , , + + + + + + + - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV good health. Chinese herbs for 14 days. The patient was otherwise in years previously, which had been treated with traditional There had been an HPZ skin lesion in the same region 2 black papules and patches, as well as petechiae (Fig. 1a). months. 3 for persisted and white exhibited patient The had which ribs, and back right her over patches like band- with presented woman 61-year-old A Case 17. Case reports below intheCase20subsection. the WIR literature, and the detailed description is given diagnosed in patient 20; this represents a novel report in noma (SEC) accompanied by bullous LSA (BLSA) was CD4 for positive was staining Immunohistochemical distributed in the region of inflammation (9/12, 75.0%). from 9 patients, we observed mast cells (MCs) diffusely staining and two patients by clinical diagnosis. In slides slide by confirmed were patients 3 (20.8%); patients 5 in found were Comedones patients. 12 in agnosis previously in WIR. dermatitis neglecta (patients 3 and 4) were not reported acne vulgaris and comedones (patient 24). Impetigo and and 19), (patient dermatitis eosinophilic 15), (patient (LSA; patient 10), comedones (patient atrophicus 14), poikiloderma et sclerosus lichen 9), (patient vitiligo 8), (patient prurigo 6), (patient keloid 23), and 5 (patients tigo (patient 3), dermatitis neglecta (patient 4), psoriasis further histopathological tests. Diagnoses included impe without findings clinical dermatologist’s a on based in two slides; one was positive. Syringoid eccrine carci 9 patients (9/10, 90.0%). CD138 staining was performed were normal. CD117 staining was positive in slides from and CD8 and Histopathological findings enabled a definitive di definitive a enabled findings Histopathological + T cells in 10 patients, and CD4 and patients, 10 in cells T + /CD8 + ratios - - - +

striatus. Histopathological examination of atrophic folli SEC accompanied by BLSA (Fig. 2b). Immunohisto 2b). (Fig. BLSA by accompanied SEC of diagnosis a to led analysis Histopathological areas. residual subcutaneousnodules. caused had which prior, year one HPZ recurrent had She then. since hypopigmentation and atrophy residual with prior, years 6 HPZ with diagnosed been had she translucent (Fig. 2a). Past medical history revealed that and thin extremely was skin surrounding The patches. hypopigmented the over bullae and vesicles, erythema, band-like well-demarcated hypopigmented patches, with had persisted for 3 weeks. Physical examination revealed erythema and bullae over the right side of her back, which 20. Case A 61-year-old woman presented with band-like given to the patient, and she underwent regular follow-up. was 1d). cream ACD117(Fig. corticosteroid and CD8, CD4, for positive was staining Immunohistochemistry diagnosis was made of BLSA and comedones after HPZ. keratin. Aby obstructed invagination follicular showed with a histological diagnosis of BLSA. In addition, slides consistent were findings These c). 1b, (Fig. appendages Perivascular lymphocyte infiltration was observed on skin incontinence. melanin and homogenisation, formation, rete ridges, vacuolar degeneration in the basal layer, cleft perkeratosis in the epidermis, atrophy and flattening of the cular lesions on the upper back showed basket-weave hy of follow-up. skin grafting, no recurrence was observed during 1-year 5%. approximately was and index resection Ki67 After The β-catenin. and 2d) (Fig. S100 2c), (Fig. 7 keratin cyto p63, actin, muscle smooth for positive were cells tumour Infiltrated CD138. and CD117, CD8, CD4, for chemistry showed inflammatory cells that were positive Her linear skin lesion was initially diagnosed as lichen Skin biopsies were taken from the bullous and nodular WIR: 24newcasesandliteraturereview for CD117. staining Positive (d) comedo. typical a of view High-power (c) mid-dermis. the in present periappendageal infiltrate is lymphocytic dense dermis; of collagen in the upper homogenisation and oedema dermal pronounced with split subepidermal a forming layer, cell basal the of degeneration atrophic epidermis with hydropic back shows typical comedo and follicular lesions on the upper the back. (b) Biopsy of atrophic petechiae on the right sideof and patches, papules, black Fig. 1. Case 17. Acta DermVenereol 2019 (a) White or 955 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta indicated that cutaneous reactions appearing at sites of sites at appearing reactions cutaneous that indicated have investigations Other (11). formation and DNAVZV of persistence the between association fected by antiviral therapy (10). Another study found no unaf is that reaction hypersensitivity delayed atypical cytopathic changes, suggesting that the virus viral induces an observed histologically no with lesions early in DNA VZV found have Researchers (5). WIR of onset Köebner’s phenomenon have been suggested to elicit the and reactions hypersensitivity IV or III type literature, the In understood. incompletely remains lesions HPZ of resolution the following WIR of pathogenesis The Mechanism andpathogenesis of Wolf’s isotopic response clearly understand WIR (Fig.3). more to clinicians enable can changes pathological on category and disease manifestation, classification based of unified labelling of WIR classification. Unlike disease the previous literature and found that there remains a lack leading to abnormal immune function. Wefactor have driving reviewed the was HPZ where changes, structural pathological local by caused were reactions WIR these adnexal carcinoma. Nevertheless, we believe that all of tions ranged from pure pigment abnormalities to dermal medical histories and ages, and their disease manifesta various had patients Our BLSA. by accompanied SEC of instance rare a and neglecta, dermatitis impetigo, include to WIR of spectrum the extended and diseases pared with previous reports, we have added several new of the second dermatosis differed from initial HPZ. Com with WIR after HPZ. A variety of clinical manifestations Our case series is unique in that we enrolled 24 patients DISCUSSION 956 T. Wangetal. - - - centripetally, sensory nerve fibres modulate the skin im of viral DNA. In addition to conducting sensorial stimuli affected dermatome, is caused by the continued influence the onset of various immunity-related disorders along the the VZV-infectedin to destabilisation leads which site, (18). Weneuroimmune of mechanism this that propose been observed in both acne (17) and bullous pemphigoid have neuropathy HPZ-induced than other neuropathy peripheral by caused disorders Immunity-related (16). dermatome affected the in control immune altering thus release, neuropeptide to related are dysfunction immune causing injury nerve of effects The (15). skin normal with compared reduced, is skin HPZ-affected previously in endings nerve epidermal of density The of lichenoid reactions in postherpetic WIR lesions (14). injury hypothesis. In this study, we found CD117 occur (e.g., insect bite reaction) may not may fit withresponses the isotopic nerve where diseases skin common other Clinically, (16). cells) Langerhans’ and cytes, lympho (MCs, cells immune of receptors membrane with interact that peptide) gene-related calcitonin and P,substance as peptide, (such intestinal tors vasoactive mune response centrifugally by secreting neuromodula memory CD8 resident of existence unrecognised previously the that suggested study One 13). 12, (5, lesions within DNA HPZ scars are not due to the presence of persistent VZV we found infections with bacteria and fungi due to local addition, In 23). and 5 (patients psoriasis and 22), and bullous morphoea (patient 11), scleroderma (patients 18 20), and 17 BLSA(patients 12), (patient planus lichen Clinically, we observed bullous pemphigoid (patient 7), dermatomes. VZV-infected in reactions immune local in 9 of 10 patients. This was representative of excessive + T cells may contribute to the pathogenesis 7. (d)Positive stainingforS100. the mid- dermis. in (c) Positive staining for glands cytokeratin infiltrating atypical as well as dermis, upper the in collagen of homogenisation and oedema pronounced dermal with split subepidermal a degeneration of Hydropicthe basal cell (b) layer forming patch. hypopigmented the over bullae and vesicles, erythema, with patch, hypopigmented demarcated Fig. 2. Case 20. a Bn-ie well- Band-like, (a) + MCs ­ - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV folliculitis (5, 25), acquired (26), granulomatous 24), (23, erythematosus lupus as such reported in the literature with the above manifestations, diseases been have there changes, follicle hair and skin with above mentioned diseases the to addition In skin. WIR in common are changes follicular and epidermal of stratum spinosum, or psoriatic hyperplasia showed that changes, such as , follicular plug, atrophy epidermal obvious diagnoses, pathological and clinical in another each from differed patients these Although poikiloderma). and vitiligo as (such melanocytes in changes pigmentation and planus, lichen psoriasis, LSA, scleroderma, neglecta, dermatitis localised with patients of reports been have there addition, In 19–22). well as acneiform eruption, at the site of healed HPZ (7, been a few reports of the development of comedones, as in 5 patients (patients 2, 14, 16, 17, and 24). There have comedones or acne typical found we series, case our In response Epidermal andfollicularchangesafterWolf’s isotopic neglecta (patient4). (patients 2 and 24), impetigo (patient 3), and dermatitis immune destabilisation including acneiform dermatosis zoster Fig. 3. Illustration of neuroimmune dysfunction-induced secondary histopathological classification in Wolf’s isotopic response after herpes (HPZ). (HPZ). LP: lichen planus; LSA: lichen sclerosus et atrophicus; BP: bullous pemphigoid; BCC: basal cell carcinoma; SCC: squamous cell carcinoma. instances of BLSA, as well as a patient with bullous with patient a as well as BLSA, of instances rare two here added Wehave 32–34). (9, morphoea of and trauma caused by viral infection can elicit the onset injuries, vascular response, immune local previously, reported As 20). and 17 (patients LSA or 19), (patient scleroderma 11), (patient morphoea bullous 13), and 6 (patients keloid collagen, of densification and dening wi proliferation, fibroblast as manifest primarily these There are few changes in dermal components after WIR; Dermal tissuechangesafterWolf’s isotopicresponse of substanceP (17). concentration the changing by lesions tissue skin local thus indicating that local nerve abnormalities can cause cheeks, the on acne and pain improves trauma after gia neural trigeminal of treatment capsaicin that reported changes at the site of healed HPZ. Similarly, it has been epidermal of development the inducing in role crucial P,substance a play might endings nerve damaged from as such neuropeptides, of release The infection. VZV after destroyed is fibres nerve of network local the that cum contagiosum (31). As we noted above, we propose (28), giant lichenification (29), poliosis (30), and mollus cyst epidermal (27), folliculitis Trichophyton rubrum WIR: 24newcasesandliteraturereview Acta DermVenereol 2019 957 - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta detected, and the CD4 CD4 and infiltration, lichenoid showed 21 and 12 Patients and CD138 and were both present at near normal ratios; this finding dif invasion in WIR are not uncommon in the literature. the in uncommon not are WIR in invasion report of SEC as a WIR. However, reports of malignant no found we PubMed, of search a In origin. eccrine of tumour adnexal malignant rare a is 20) (patient SEC Malignant invasionsinWolf’s isotopicresponse matory cells. inflam above the of infiltration as well as chemokines, other and interleukin-4 of secretion the to lead may damage and residual virus particles after virus infection nerve that speculate we Therefore, 45). 12, (4, matous pilaris; CD117 after HPZ. lesions skin in roles key play MCs that speculate We (42). 12) (patient planus lichen and 41), (5, 7) (patient keloid (patients 6 and 13) (39, 40), bullous pemphigoid cause disease; these include psoriasis (patient 5) (36–38), can that mediators inflammatory and cytokines various release and produce they because skin the in responses immune and processes pathophysiological many in involved are MCs However, studies. previous in sed CD8 were epidermis the in lymphocytes most that found (14) al. et Ise reports. previous of that from fers CD4 Both patients. 10 from We slides biopsy in infiltrations inflammatory explored Inflammatory infiltrationsin Wolf’s isotopic response but itspathogenesisisunknown(35). reported, been has Mucinosis fibroblasts. by produced mucin is tissue dermal in component major Another pathogenesis. similar a have might these scleroderma; 958 in previousstudies. found in patients 3, 7, 19, and 24 in our study, as well as Moreover, eosinophils (43, 44) and neutrophils (14) were infiltration might differ, as clinical manifestations varied. while approximately equal numbers of CD4 MCs infiltrating the WIR lesion, which was not addres infiltration duringprogressionofinflammation. these two studies may reflect differences in lymphocyte between differences the Thus, regression. of stage the approaching darkened, and small were papules red the 21, and 12 However,patients fused. in rarely were that papules red many with presented patient former The study. present the in 21 and 12 patients in those with reaction. We compared the clinical features in Ise’s report lichenoid a in dermis the in detected were lymphocytes cell infiltration was detected. In patient 20, CD117 However, in patient 21, the slides showed lichen plano Most inflammatory infiltrations in WIR are granulo are WIR in infiltrations inflammatory Most Nine of 10 patients’ slides in our study showed CD117 + and CD8 and T. Wangetal. + plasma cells revealed that inflammatory that revealed cells plasma + MCs were negative, but CD138 + T cells in the epidermis and dermis and epidermis the in cells T + /CD8 + T-cell ratios were normal. + and CD8 and + T cells were cells T + and CD8 + plasma + MCs + - - - - - + + ,

REFERENCES The authorshavenoconflicts of interest todeclare. ABD02-201709. Research Funds for the Central Universities (3332018025); NCMI- cn/ac), foreditingtheEnglishtextofdraftsthismanuscript. PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji. Kerr, BSc, PhD, Gillian Campbell, Cathel PhD, thank and Ryan also Chastain-Gross, We making. figure and illustration with help The authors thank Guangzhou Sagene Biotech Co., Ltd. for their ACKNOWLEDGEMENTS with malignantdiseases. associated be may it that possibility the of because tion clinical phenomenon, WIR should receive greater atten groups based on dermatopathological 4 changes. As into a rare WIR classified and literature the reviewed We WIR. of definition the in included previously not were 24 patients with WIR, including some with diseases that (16). Weof WIR occurrence the induce described have might sites infection VZV at instability neuroimmune sease (48). The pathogenesis of WIR is di not yet first clear,the by and left changes minimal other or changes, condary disease at the site of a superficial , pigment WIR is a specific phenomenon that is defined as a se as defined is that phenomenon specific a is WIR Conclusion studies onthisphenomenonareneededinthefuture. may receive a diagnosis of WIR; thus, additional in-depth WIR is given closer attention by clinicians, more patients When diseases. primary previous regarding recall poor patients’ of because partly and disease, this regarding clinical practice, partly because of the lack of knowledge associated with these cells in WIR. WIR is uncommon in we did not assess the mechanism of inflammatory factors cells, plasma and MCs in CD138 and CD117 detected performed. be we not Although could neuropeptides or assessments of VZV-DNA,of assessments CD8 immunohistochemical examinations were limited; thus, and the numbers of specimens for histopathological and The number of patients included in our study was small, Limitations to excludeneoplasm(4,46,47). treatments, we suggest that biopsy should be performed cutis (1). Instead of administering antiviral drugs or other metastasis, Bowen’s disease, lymphoma, and leukaemia squamous carcinoma, Kaposi’s sarcoma, angiosarcoma, baso­ carcinoma, cell squamous carcinoma, cell basal carcinoma, breast including disease, malignant had 35 Wolf et al. reviewed and reported 66 patients with WIR; 1. This work was supported by the grants from the Fundamental the from grants the by supported was work This Wolf R, Brenner S, Ruocco V, Filioli FG. Isotopic response. Isotopic FG. 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